Variant chr1-161524779-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002155.5(HSPA6):c.121C>A(p.Pro41Thr) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00063 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00044 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

HSPA6
NM_002155.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.18

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026300788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA6	NM_002155.5 linkuse as main transcript	c.121C>A	p.Pro41Thr	missense_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.121C>A	p.Pro41Thr	missense_variant	1/1	6	NM_002155.5	ENSP00000310219.4		P17066
ENSG00000273112	ENST00000537821.2 linkuse as main transcript	n.271+6642C>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000634

AC:

AN:

151344

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000535

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000724

Gnomad ASJ

AF:

0.00549

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000420

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000590

Gnomad OTH

AF:

0.000482

GnomAD3 exomes

AF:

0.000751

AC:

117

AN:

155858

Hom.:

AF XY:

0.000622

AC XY:

AN XY:

85146

show subpopulations

Gnomad AFR exome

AF:

0.000521

Gnomad AMR exome

AF:

0.000868

Gnomad ASJ exome

AF:

0.00505

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000376

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000577

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000441

AC:

624

AN:

1416500

Hom.:

Cov.:

AF XY:

0.000448

AC XY:

315

AN XY:

702832

show subpopulations

Gnomad4 AFR exome

AF:

0.000553

Gnomad4 AMR exome

AF:

0.000770

Gnomad4 ASJ exome

AF:

0.00482

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.000288

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000329

Gnomad4 OTH exome

AF:

0.000887

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000634

AC:

AN:

151460

Hom.:

Cov.:

AF XY:

0.000622

AC XY:

AN XY:

73990

show subpopulations

Gnomad4 AFR

AF:

0.000534

Gnomad4 AMR

AF:

0.000723

Gnomad4 ASJ

AF:

0.00549

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000420

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000590

Gnomad4 OTH

AF:

0.000477

Alfa

AF:

0.000899

Hom.:

Bravo

AF:

0.000638

ExAC

AF:

0.000356

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

The c.121C>A (p.P41T) alteration is located in exon 1 (coding exon 1) of the HSPA6 gene. This alteration results from a C to A substitution at nucleotide position 121, causing the proline (P) at amino acid position 41 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.018

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.93

MutationAssessor

Pathogenic

5.3

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.5

REVEL

Benign

0.24

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.76

MVP

0.59

ClinPred

0.12

GERP RS

2.3

Varity_R

0.92

gMVP

0.85

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