6-158111064-ACT-A

Position:

• chr6-158111064-ACT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_032861.4(SERAC1):​c.*300_*301del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00751 in 195,730 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (1 hom.)
• Consequence: SERAC1 NM_032861.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.512

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-158111064-ACT-A is Benign according to our data. Variant chr6-158111064-ACT-A is described in ClinVar as [Likely_benign]. Clinvar id is 1211760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00916 (1393/152114) while in subpopulation AFR AF= 0.0318 (1321/41492). AF 95% confidence interval is 0.0304. There are 23 homozygotes in gnomad4. There are 666 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERAC1	NM_032861.4	c.*300_*301del		3_prime_UTR_variant	17/17	ENST00000647468.2	NP_116250.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERAC1	ENST00000647468.2	c.*300_*301del		3_prime_UTR_variant	17/17		NM_032861.4	ENSP00000496731	P1

Frequencies

GnomAD3 genomes AF: 0.00916 AC: 1392 AN: 151998 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.00174 AC: 76 AN: 43616 Hom.: 1 AF XY: 0.00147 AC XY: 32 AN XY: 21830

Gnomad4 AFR exome AF: 0.0349

Gnomad4 AMR exome AF: 0.00263

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000708

Gnomad4 OTH exome AF: 0.00289

GnomAD4 genome AF: 0.00916 AC: 1393 AN: 152114 Hom.: 23 Cov.: 32 AF XY: 0.00896 AC XY: 666 AN XY: 74356

Gnomad4 AFR AF: 0.0318

Gnomad4 AMR AF: 0.00354

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00776 Hom.: 4

Bravo AF: 0.0106

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs148102913; hg19: chr6-158532096;