chr10-116675169-T-C

Position:

• chr10-116675169-T-C

Variant summary

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

The NM_025015.3(HSPA12A):​c.1640A>G​(p.Glu547Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,604 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: 6.8e-7 (0 hom.)
• Consequence: HSPA12A NM_025015.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.58

Genes affected

HSPA12A (HGNC:19022): (heat shock protein family A (Hsp70) member 12A) Predicted to enable ATP binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

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	Protein	UniProt
HSPA12A	NM_025015.3	c.1640A>G	p.Glu547Gly	missense_variant	12/12	ENST00000369209.8	NP_079291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA12A	ENST00000369209.8	c.1640A>G	p.Glu547Gly	missense_variant	12/12	1	NM_025015.3	ENSP00000358211.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461604 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727122

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.: 33

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

Oct 17, 2024

The c.1640A>G (p.E547G) alteration is located in exon 12 (coding exon 12) of the HSPA12A gene. This alteration results from a A to G substitution at nucleotide position 1640, causing the glutamic acid (E) at amino acid position 547 to be replaced by a glycine (G). 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	0.31
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.8	D;.
REVEL	Benign	0.22
Sift	Benign	0.23	T;.
Sift4G	Benign	0.22	T;.
Polyphen		0.42	B;.
Vest4		0.69
MutPred		0.52		Loss of catalytic residue at E547 (P = 0.0423);.;
MVP		0.093
MPC		0.94
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.32
gMVP		0.71

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: chr10-118434680;