6-31829422-C-T

Position:

• chr6-31829422-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005346.6(HSPA1B):​c.1472C>T​(p.Thr491Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 11)
  • Exomes 𝑓: 0.0000039 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSPA1B NM_005346.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0410

Genes affected

HSPA1B (HGNC:5233): (heat shock protein family A (Hsp70) member 1B) This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins. [provided by RefSeq, Jul 2008]

ENSG00000285565 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11205998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA1B	NM_005346.6	c.1472C>T	p.Thr491Met	missense_variant	1/1	ENST00000375650.5	NP_005337.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA1B	ENST00000375650.5	c.1472C>T	p.Thr491Met	missense_variant	1/1	6	NM_005346.6	ENSP00000364801.3
ENSG00000285565	ENST00000649802.1	n.589C>T		non_coding_transcript_exon_variant	1/4

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000386 AC: 4 AN: 1035172 Hom.: 0 Cov.: 14 AF XY: 0.00000193 AC XY: 1 AN XY: 518170

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: 0.0000225

Gnomad4 NFE exome AF: 0.00000394

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 11

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.062	N
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.91	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.028
Sift	Benign	0.11	T
Sift4G	Benign	0.10	T
Vest4		0.052
MutPred		0.18		Gain of MoRF binding (P = 0.0673);
MVP		0.26
ClinPred		0.090	T
GERP RS		0.32
Varity_R		0.055
gMVP		0.14

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: chr6-31797199;