3-128052316-G-A

Position:

• chr3-128052316-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001400328.1(SEC61A1):​c.25+406G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 363,824 control chromosomes in the GnomAD database, including 82,345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (28791 hom., cov: 32)
  • Exomes 𝑓: 0.71 (53554 hom.)
• Consequence: SEC61A1 NM_001400328.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.886

Genes affected

SEC61A1 (HGNC:18276): (SEC61 translocon subunit alpha 1) The protein encoded by this gene belongs to the SECY/SEC61- alpha family. It appears to play a crucial role in the insertion of secretory and membrane polypeptides into the endoplasmic reticulum. This protein found to be tightly associated with membrane-bound ribosomes, either directly or through adaptor proteins. This gene encodes an alpha subunit of the heteromeric SEC61 complex, which also contains beta and gamma subunits. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 3-128052316-G-A is Benign according to our data. Variant chr3-128052316-G-A is described in ClinVar as [Benign]. Clinvar id is 1272964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC61A1	NM_001400328.1	c.25+406G>A		intron_variant			NP_001387257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC61A1	ENST00000464451.5	c.25+406G>A		intron_variant		2		ENSP00000418493.1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 92910 AN: 150278 Hom.: 28760 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.631

GnomAD4 exome AF: 0.707 AC: 150871 AN: 213438 Hom.: 53554 AF XY: 0.706 AC XY: 71934 AN XY: 101954

Gnomad4 AFR exome AF: 0.744

Gnomad4 AMR exome AF: 0.735

Gnomad4 ASJ exome AF: 0.625

Gnomad4 EAS exome AF: 0.855

Gnomad4 SAS exome AF: 0.653

Gnomad4 FIN exome AF: 0.685

Gnomad4 NFE exome AF: 0.707

Gnomad4 OTH exome AF: 0.705

GnomAD4 genome AF: 0.618 AC: 92992 AN: 150386 Hom.: 28791 Cov.: 32 AF XY: 0.615 AC XY: 45171 AN XY: 73416

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.803

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.632

Alfa AF: 0.611 Hom.: 3541

Bravo AF: 0.632

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 02, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.3
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs74501258; hg19: chr3-127771159;