10-14839935-G-A

Variant summary

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

The NM_016299.4(HSPA14):c.88G>A(p.Ala30Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSPA14 NM_016299.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.15

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]

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

ACMG classification

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	UniProt
HSPA14	NM_016299.4	c.88G>A	p.Ala30Thr	missense_variant	2/14	ENST00000378372.8
MSANTD7	NM_001378785.1	c.-285G>A		5_prime_UTR_variant	2/5	ENST00000640019.3
MSANTD7	NM_001378790.1	c.-214G>A		5_prime_UTR_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA14	ENST00000378372.8	c.88G>A	p.Ala30Thr	missense_variant	2/14	1	NM_016299.4	P1
MSANTD7	ENST00000640019.3	c.-285G>A		5_prime_UTR_variant	2/5	1	NM_001378785.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2022

The c.88G>A (p.A30T) alteration is located in exon 2 (coding exon 2) of the HSPA14 gene. This alteration results from a G to A substitution at nucleotide position 88, causing the alanine (A) at amino acid position 30 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	Benign	0.19
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
Cadd	Pathogenic	28
Dann	Pathogenic	1.0
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-0.59	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.0	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.059	T;D
Sift4G	Uncertain	0.056	T;T
Polyphen		0.99	D;D
Vest4		0.49
MutPred		0.57		Gain of phosphorylation at A30 (P = 0.0747);Gain of phosphorylation at A30 (P = 0.0747);
MVP		0.27
MPC		0.89
ClinPred		0.95	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-14881934;