rs6929274

Positions:

• chr6-158150469-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.304

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id is 139093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-158150469-G-A is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
SERAC1	NM_032861.4	c.249C>T	p.Asp83Asp	synonymous_variant	4/17	ENST00000647468.2	NP_116250.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERAC1	ENST00000647468.2	c.249C>T	p.Asp83Asp	synonymous_variant	4/17		NM_032861.4	ENSP00000496731.1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 109013 AN: 151936 Hom.: 39201 Cov.: 32

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

GnomAD3 exomes AF: 0.724 AC: 178863 AN: 247092 Hom.: 65195 AF XY: 0.718 AC XY: 95963 AN XY: 133588

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 SAS exome AF: 0.669

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.: 29 AF XY: 0.707 AC XY: 495198 AN XY: 700360

Gnomad4 AFR exome AF: 0.707

Gnomad4 AMR exome AF: 0.843

Gnomad4 ASJ exome AF: 0.735

Gnomad4 EAS exome AF: 0.796

Gnomad4 SAS exome AF: 0.671

Gnomad4 FIN exome AF: 0.711

Gnomad4 NFE exome AF: 0.702

Gnomad4 OTH exome AF: 0.710

GnomAD4 genome AF: 0.718 AC: 109116 AN: 152054 Hom.: 39245 Cov.: 32 AF XY: 0.718 AC XY: 53390 AN XY: 74316

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.706

Gnomad4 OTH AF: 0.720

Alfa AF: 0.708 Hom.: 60647

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

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 2013	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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 -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided Benign:1

Benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Feb 19, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.7
DANN	Benign	0.42

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

LitVar

Other links and lift over

dbSNP: rs6929274; hg19: chr6-158571501;