Variant chr6-31816809-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_005345.6(HSPA1A):c.1053G>A(p.Gln351=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HSPA1A
NM_005345.6 synonymous

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 0.527

Variant links:

Genes affected

HSPA1A (HGNC:5232): (heat shock protein family A (Hsp70) member 1A) This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins. [provided by RefSeq, Jul 2008]

HSPA1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP7

Synonymous conserved (PhyloP=0.527 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA1A	NM_005345.6 linkuse as main transcript	c.1053G>A	p.Gln351=	synonymous_variant	1/1	ENST00000375651.7	NP_005336.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA1A	ENST00000375651.7 linkuse as main transcript	c.1053G>A	p.Gln351=	synonymous_variant	1/1		NM_005345.6	ENSP00000364802	P1	P0DMV8-1
HSPA1A	ENST00000608703.1 linkuse as main transcript	c.558G>A	p.Gln186=	synonymous_variant	2/2	2		ENSP00000477378

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0150

AC:

1431

AN:

95294

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

766

AN XY:

50784

show subpopulations

Gnomad4 AFR exome

AF:

0.00268

Gnomad4 AMR exome

AF:

0.00746

Gnomad4 ASJ exome

AF:

0.0269

Gnomad4 EAS exome

AF:

0.0142

Gnomad4 SAS exome

AF:

0.0206

Gnomad4 FIN exome

AF:

0.00964

Gnomad4 NFE exome

AF:

0.0149

Gnomad4 OTH exome

AF:

0.0136

GnomAD4 genome

Cov.:

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Chronic obstructive pulmonary disease

Other:1

association, no assertion criteria provided

case-control

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Aug 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

9.0

DANN

Benign

0.93

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over