rs6929274

Variant names:

• chr6-158150469-G-A
• rs6929274
• NM_032861.4:c.249C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 publications found

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: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, G2P
• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032861.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERAC1	NM_032861.4	MANE Select	c.249C>T	p.Asp83Asp	synonymous	Exon 4 of 17	NP_116250.3
	SERAC1	NR_073096.2		n.373C>T		non_coding_transcript_exon	Exon 4 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERAC1	ENST00000647468.2	MANE Select	c.249C>T	p.Asp83Asp	synonymous	Exon 4 of 17	ENSP00000496731.1	Q96JX3-1
	SERAC1	ENST00000606965.5	TSL:1	n.249C>T		non_coding_transcript_exon	Exon 4 of 13	ENSP00000475808.1	U3KQE4
	SERAC1	ENST00000607742.5	TSL:1	n.*83C>T		non_coding_transcript_exon	Exon 3 of 15	ENSP00000475523.1	U3KQG3

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

GnomAD2 exomes AF: 0.724 AC: 178863 AN: 247092 AF XY: 0.718

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

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

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

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

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.7
DANN	Benign	0.42
PhyloP100		0.30
Mutation Taster		=84/16	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6929274; hg19: chr6-158571501; COSMIC: COSV108214273;