chr1-161524770-C-A

Position:

• chr1-161524770-C-A

Variant summary

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

The NM_002155.5(HSPA6):​c.112C>A​(p.Arg38Ser) variant causes a missense change involving the alteration of a non-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: 31)
• Consequence: HSPA6 NM_002155.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.482

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]

ENSG00000273112 (HGNC:):

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
HSPA6	NM_002155.5	c.112C>A	p.Arg38Ser	missense_variant	1/1	ENST00000309758.6	NP_002146.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA6	ENST00000309758.6	c.112C>A	p.Arg38Ser	missense_variant	1/1	6	NM_002155.5	ENSP00000310219.4
ENSG00000273112	ENST00000537821.2	n.271+6633C>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Nov 08, 2022

The c.112C>A (p.R38S) 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 112, causing the arginine (R) at amino acid position 38 to be replaced by a serine (S). 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	0.98
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	4.0	H
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.51
MutPred		0.67		Gain of glycosylation at R38 (P = 0.0162);
MVP		0.48
ClinPred		0.94	D
GERP RS		2.5
Varity_R		0.80
gMVP		0.58

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: chr1-161494560;