chr6-158148854-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032861.4(SERAC1):c.355+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,575,790 control chromosomes in the GnomAD database, including 180,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14960 hom., cov: 33)

Exomes 𝑓: 0.48 ( 165598 hom. )

Consequence

SERAC1
NM_032861.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.157

Publications

11 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 6-158148854-T-C is Benign according to our data. Variant chr6-158148854-T-C is described in ClinVar as Benign. ClinVar VariationId is 139094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERAC1	NM_032861.4 link	c.355+11A>G		intron_variant	Intron 5 of 16	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.355+11A>G		intron_variant	Intron 5 of 16		NM_032861.4	ENSP00000496731.1		Q96JX3-1

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65294

AN:

152044

Hom.:

14933

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.595

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.453

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.446

GnomAD2 exomes

AF:

0.481

AC:

117002

AN:

243458

AF XY:

0.479

show subpopulations

Gnomad AFR exome

AF:

0.262

Gnomad AMR exome

AF:

0.667

Gnomad ASJ exome

AF:

0.527

Gnomad EAS exome

AF:

0.421

Gnomad FIN exome

AF:

0.456

Gnomad NFE exome

AF:

0.477

Gnomad OTH exome

AF:

0.499

GnomAD4 exome

AF:

0.478

AC:

679924

AN:

1423628

Hom.:

165598

Cov.:

AF XY:

0.478

AC XY:

338929

AN XY:

709540

show subpopulations

African (AFR)

AF:

0.258

AC:

8401

AN:

32514

American (AMR)

AF:

0.661

AC:

28450

AN:

43044

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

13589

AN:

25756

East Asian (EAS)

AF:

0.491

AC:

19261

AN:

39260

South Asian (SAS)

AF:

0.449

AC:

37187

AN:

82864

European-Finnish (FIN)

AF:

0.455

AC:

24249

AN:

53250

Middle Eastern (MID)

AF:

0.538

AC:

3058

AN:

5688

European-Non Finnish (NFE)

AF:

0.479

AC:

518490

AN:

1082176

Other (OTH)

AF:

0.461

AC:

27239

AN:

59076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

15244

30488

45733

60977

76221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15134

30268

45402

60536

75670

<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:

0.430

AC:

65357

AN:

152162

Hom.:

14960

Cov.:

AF XY:

0.432

AC XY:

32145

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.267

AC:

11066

AN:

41516

American (AMR)

AF:

0.596

AC:

9114

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

1799

AN:

3470

East Asian (EAS)

AF:

0.432

AC:

2242

AN:

5186

South Asian (SAS)

AF:

0.434

AC:

2095

AN:

4826

European-Finnish (FIN)

AF:

0.453

AC:

4794

AN:

10576

Middle Eastern (MID)

AF:

0.548

AC:

160

AN:

292

European-Non Finnish (NFE)

AF:

0.483

AC:

32857

AN:

67984

Other (OTH)

AF:

0.449

AC:

948

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1877

3754

5631

7508

9385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.472

Hom.:

9828

Bravo

AF:

0.434

Asia WGS

AF:

0.417

AC:

1449

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

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 -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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. -

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

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.7

(source)

DANN

Benign

0.42

PhyloP100

0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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