Variant chr10-14838451-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000378372.8(HSPA14):c.49G>C(p.Val17Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,244 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HSPA14
ENST00000378372.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

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:

MSANTD7 (HGNC:56248): (Myb/SANT DNA binding domain containing 7)

MSANTD7 links:

CDNF (HGNC:24913): (cerebral dopamine neurotrophic factor) Predicted to enable growth factor activity. Predicted to be involved in dopaminergic neuron differentiation and neuron projection development. Predicted to be active in endoplasmic reticulum and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

CDNF links:

MSANTD7 (HGNC:):

MSANTD7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA14	NM_016299.4 linkuse as main transcript	c.49G>C	p.Val17Leu	missense_variant	1/14	ENST00000378372.8	NP_057383.2	Q0VDF9
MSANTD7	NM_001378785.1 linkuse as main transcript	c.-324G>C		5_prime_UTR_variant	1/5	ENST00000640019.3	NP_001365714.1
MSANTD7	NM_001378790.1 linkuse as main transcript	c.-253G>C		5_prime_UTR_variant	1/4		NP_001365719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA14	ENST00000378372.8 linkuse as main transcript	c.49G>C	p.Val17Leu	missense_variant	1/14	1	NM_016299.4	ENSP00000367623.3		Q0VDF9
MSANTD7	ENST00000640019.3 linkuse as main transcript	c.-324G>C		5_prime_UTR_variant	1/5	1	NM_001378785.1	ENSP00000491568.1		A0A1W2PQ72

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1452244

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721954

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

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

Feb 05, 2024

The c.49G>C (p.V17L) alteration is located in exon 1 (coding exon 1) of the HSPA14 gene. This alteration results from a G to C substitution at nucleotide position 49, causing the valine (V) at amino acid position 17 to be replaced by a leucine (L). 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

0.32

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.068

.;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.42

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.9

.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.7

D;N

REVEL

Benign

0.19

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.016

D;D

Polyphen

0.46

P;P

Vest4

0.57

MutPred

0.80

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.36

MPC

0.35

ClinPred

0.89

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.66

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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