Variant chr10-14867252-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016299.4(HSPA14):c.1163A>T(p.Asp388Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,524 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HSPA14
NM_016299.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.49

Variant links:

Genes affected

HSPA14 (HGNC:29526): (heat shock protein family A (Hsp70) member 14) Predicted to enable several functions, including ATP binding activity; misfolded protein binding activity; and unfolded protein binding activity. Predicted to be involved in several processes, including cellular response to unfolded protein; chaperone cofactor-dependent protein refolding; and protein refolding. Located in cytosol. Colocalizes with ribosome. [provided by Alliance of Genome Resources, Apr 2022]

HSPA14 links:

SUV39H2-DT (HGNC:55188): (SUV39H2 divergent transcript)

SUV39H2-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23124719).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA14	NM_016299.4 link	c.1163A>T	p.Asp388Val	missense_variant	11/14	ENST00000378372.8	NP_057383.2	Q0VDF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA14	ENST00000378372.8 link	c.1163A>T	p.Asp388Val	missense_variant	11/14	1	NM_016299.4	ENSP00000367623.3		Q0VDF9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251238

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461524

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 20, 2024

The c.1163A>T (p.D388V) alteration is located in exon 11 (coding exon 11) of the HSPA14 gene. This alteration results from a A to T substitution at nucleotide position 1163, causing the aspartic acid (D) at amino acid position 388 to be replaced by a valine (V). 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

Benign

0.29

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

M_CAP

Benign

0.037

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.9

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.010

Polyphen

0.012

Vest4

0.37

MutPred

0.60

Loss of sheet (P = 0.0084);

MVP

0.27

MPC

0.90

ClinPred

1.0

GERP RS

6.0

Varity_R

0.81

gMVP

0.75

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