6-158146034-A-T

Variant names:

• chr6-158146034-A-T
• rs9295316
• NM_032861.4:c.487+748T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032861.4(SERAC1):​c.487+748T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,262 control chromosomes in the GnomAD database, including 2,504 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (2504 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: SERAC1 NM_032861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERAC1	NM_032861.4	c.487+748T>A		intron_variant	Intron 6 of 16	ENST00000647468.2	NP_116250.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERAC1	ENST00000647468.2	c.487+748T>A		intron_variant	Intron 6 of 16		NM_032861.4	ENSP00000496731.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21937 AN: 152140 Hom.: 2484 Cov.: 32

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 AFR exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.144 AC: 21971 AN: 152258 Hom.: 2504 Cov.: 32 AF XY: 0.152 AC XY: 11290 AN XY: 74442

Gnomad4 AFR AF: 0.0352

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.152

Alfa AF: 0.0574 Hom.: 79

Bravo AF: 0.154

Asia WGS AF: 0.270 AC: 934 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.65

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: rs9295316; hg19: chr6-158567066;