Variant 6-31817466-G-T 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.1710G>T(p.Val570=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.013 ( 28 hom., cov: 31)

Exomes 𝑓: 0.0036 ( 280 hom. )

Failed GnomAD Quality Control

Consequence

HSPA1A
NM_005345.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.589

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=-0.67).

BP7

Synonymous conserved (PhyloP=-0.589 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.1710G>T	p.Val570=	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.1710G>T	p.Val570=	synonymous_variant	1/1		NM_005345.6	ENSP00000364802	P1	P0DMV8-1
HSPA1A	ENST00000608703.1 linkuse as main transcript	c.1215G>T	p.Val405=	synonymous_variant	2/2	2		ENSP00000477378

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1894

AN:

151486

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0154

Gnomad ASJ

AF:

0.0616

Gnomad EAS

AF:

0.0141

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00841

Gnomad OTH

AF:

0.0189

GnomAD3 exomes

AF:

0.00132

AC:

322

AN:

243216

Hom.:

AF XY:

0.00155

AC XY:

206

AN XY:

132476

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.000881

Gnomad ASJ exome

AF:

0.00493

Gnomad EAS exome

AF:

0.00190

Gnomad SAS exome

AF:

0.00336

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000685

Gnomad OTH exome

AF:

0.00218

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00356

AC:

5147

AN:

1446544

Hom.:

280

Cov.:

AF XY:

0.00367

AC XY:

2636

AN XY:

719022

show subpopulations

Gnomad4 AFR exome

AF:

0.00496

Gnomad4 AMR exome

AF:

0.00400

Gnomad4 ASJ exome

AF:

0.0321

Gnomad4 EAS exome

AF:

0.0355

Gnomad4 SAS exome

AF:

0.00280

Gnomad4 FIN exome

AF:

0.00126

Gnomad4 NFE exome

AF:

0.00168

Gnomad4 OTH exome

AF:

0.00624

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0125

AC:

1898

AN:

151604

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

928

AN XY:

74074

show subpopulations

Gnomad4 AFR

AF:

0.0158

Gnomad4 AMR

AF:

0.0154

Gnomad4 ASJ

AF:

0.0616

Gnomad4 EAS

AF:

0.0142

Gnomad4 SAS

AF:

0.0203

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00841

Gnomad4 OTH

AF:

0.0187

Alfa

AF:

0.00463

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.4

DANN

Benign

0.94

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over