Variant chr1-161524805-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002155.5(HSPA6):c.147C>G(p.Thr49Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000862 in 150,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00067 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

HSPA6
NM_002155.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.19

Variant links:

Genes affected

HSPA6 (HGNC:5239): (heat shock protein family A (Hsp70) member 6) Enables enzyme binding activity; heat shock protein binding activity; and unfolded protein binding activity. Involved in cellular response to heat and protein refolding. Located in centriole and cytosol. Colocalizes with COP9 signalosome. [provided by Alliance of Genome Resources, Apr 2022]

HSPA6 links:

ENSG00000273112 (HGNC:):

ENSG00000273112 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 1-161524805-C-G is Benign according to our data. Variant chr1-161524805-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2639512.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.19 with no splicing effect.

BS2

High AC in GnomAd4 at 130 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA6	NM_002155.5 linkuse as main transcript	c.147C>G	p.Thr49Thr	synonymous_variant	1/1	ENST00000309758.6	NP_002146.2	P17066A0A384NKX5B3KSM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA6	ENST00000309758.6 linkuse as main transcript	c.147C>G	p.Thr49Thr	synonymous_variant	1/1	6	NM_002155.5	ENSP00000310219.4		P17066
ENSG00000273112	ENST00000537821.2 linkuse as main transcript	n.271+6668C>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000856

AC:

129

AN:

150768

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000265

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000972

Gnomad SAS

AF:

0.000635

Gnomad FIN

AF:

0.00257

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000622

Gnomad OTH

AF:

0.00146

GnomAD3 exomes

AF:

0.000835

AC:

153

AN:

183306

Hom.:

AF XY:

0.000873

AC XY:

AN XY:

100822

show subpopulations

Gnomad AFR exome

AF:

0.000859

Gnomad AMR exome

AF:

0.000716

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000798

Gnomad SAS exome

AF:

0.000765

Gnomad FIN exome

AF:

0.00177

Gnomad NFE exome

AF:

0.000815

Gnomad OTH exome

AF:

0.000825

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000667

AC:

963

AN:

1442956

Hom.:

Cov.:

AF XY:

0.000647

AC XY:

464

AN XY:

716986

show subpopulations

Gnomad4 AFR exome

AF:

0.00127

Gnomad4 AMR exome

AF:

0.000647

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000510

Gnomad4 SAS exome

AF:

0.000576

Gnomad4 FIN exome

AF:

0.00202

Gnomad4 NFE exome

AF:

0.000616

Gnomad4 OTH exome

AF:

0.000654

GnomAD4 genome

AF:

0.000862

AC:

130

AN:

150882

Hom.:

Cov.:

AF XY:

0.000977

AC XY:

AN XY:

73670

show subpopulations

Gnomad4 AFR

AF:

0.00112

Gnomad4 AMR

AF:

0.000264

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000975

Gnomad4 SAS

AF:

0.000635

Gnomad4 FIN

AF:

0.00257

Gnomad4 NFE

AF:

0.000622

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.00316

Hom.:

Bravo

AF:

0.000563

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

HSPA6: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

4.4

DANN

Benign

0.57

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