rs6929274

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032861.4(SERAC1):c.249C>T(p.Asp83Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,554,476 control chromosomes in the GnomAD database, including 393,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 39245 hom., cov: 32)

Exomes 𝑓: 0.71 ( 353856 hom. )

Consequence

SERAC1
NM_032861.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.304

Publications

27 publications found

Variant links:

Genes affected

SERAC1 (HGNC:21061): (serine active site containing 1) The protein encoded by this gene is a phosphatidylglycerol remodeling protein found at the interface of mitochondria and endoplasmic reticula, where it mediates phospholipid exchange. The encoded protein plays a major role in mitochondrial function and intracellular cholesterol trafficking. Defects in this gene are a cause of 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL). Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Aug 2012]

SERAC1 Gene-Disease associations (from GenCC):

3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
Leigh syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

SERAC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 6-158150469-G-A is Benign according to our data. Variant chr6-158150469-G-A is described in ClinVar as Benign. ClinVar VariationId is 139093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.304 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERAC1	NM_032861.4 link	c.249C>T	p.Asp83Asp	synonymous_variant	Exon 4 of 17	ENST00000647468.2	NP_116250.3	Q96JX3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERAC1	ENST00000647468.2 link	c.249C>T	p.Asp83Asp	synonymous_variant	Exon 4 of 17		NM_032861.4	ENSP00000496731.1		Q96JX3-1

Frequencies

GnomAD3 genomes

AF:

0.717

AC:

109013

AN:

151936

Hom.:

39201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.710

Gnomad AMI

AF:

0.659

Gnomad AMR

AF:

0.800

Gnomad ASJ

AF:

0.729

Gnomad EAS

AF:

0.733

Gnomad SAS

AF:

0.667

Gnomad FIN

AF:

0.715

Gnomad MID

AF:

0.775

Gnomad NFE

AF:

0.706

Gnomad OTH

AF:

0.720

GnomAD2 exomes

AF:

0.724

AC:

178863

AN:

247092

AF XY:

0.718

show subpopulations

Gnomad AFR exome

AF:

0.709

Gnomad AMR exome

AF:

0.848

Gnomad ASJ exome

AF:

0.736

Gnomad EAS exome

AF:

0.719

Gnomad FIN exome

AF:

0.712

Gnomad NFE exome

AF:

0.706

Gnomad OTH exome

AF:

0.718

GnomAD4 exome

AF:

0.708

AC:

993389

AN:

1402422

Hom.:

353856

Cov.:

AF XY:

0.707

AC XY:

495198

AN XY:

700360

show subpopulations

African (AFR)

AF:

0.707

AC:

22756

AN:

32172

American (AMR)

AF:

0.843

AC:

36815

AN:

43652

Ashkenazi Jewish (ASJ)

AF:

0.735

AC:

18818

AN:

25610

East Asian (EAS)

AF:

0.796

AC:

31353

AN:

39368

South Asian (SAS)

AF:

0.671

AC:

56236

AN:

83848

European-Finnish (FIN)

AF:

0.711

AC:

37110

AN:

52212

Middle Eastern (MID)

AF:

0.712

AC:

4017

AN:

5644

European-Non Finnish (NFE)

AF:

0.702

AC:

744829

AN:

1061500

Other (OTH)

AF:

0.710

AC:

41455

AN:

58416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

11714

23427

35141

46854

58568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18518

37036

55554

74072

92590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.718

AC:

109116

AN:

152054

Hom.:

39245

Cov.:

AF XY:

0.718

AC XY:

53390

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.710

AC:

29423

AN:

41442

American (AMR)

AF:

0.800

AC:

12229

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.729

AC:

2525

AN:

3466

East Asian (EAS)

AF:

0.734

AC:

3798

AN:

5176

South Asian (SAS)

AF:

0.667

AC:

3217

AN:

4822

European-Finnish (FIN)

AF:

0.715

AC:

7543

AN:

10552

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.706

AC:

48035

AN:

67996

Other (OTH)

AF:

0.720

AC:

1520

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1580

3160

4741

6321

7901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

840

1680

2520

3360

4200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.710

Hom.:

74741

Bravo

AF:

0.723

Asia WGS

AF:

0.716

AC:

2487

AN:

3476

EpiCase

AF:

0.714

EpiControl

AF:

0.715

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Sep 05, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Feb 19, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.7

(source)

DANN

Benign

0.42

PhyloP100

0.30

Mutation Taster

=84/16

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over