rs200964846

Variant names:

• chr13-31148091-C-A
• rs200964846
• NM_006644.4:c.1246G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-31148091-C-A
• chr13-31148091-C-T

Variant summary

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

The NM_006644.4(HSPH1):​c.1246G>T​(p.Val416Phe) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSPH1 NM_006644.4 missense, splice_region
• Scores: Splicing: ADA: 0.5071
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

Genes affected

HSPH1 (HGNC:16969): (heat shock protein family H (Hsp110) member 1) This gene encodes a member of the heat shock protein 70 family of proteins. The encoded protein functions as a nucleotide exchange factor for the molecular chaperone heat shock cognate 71 kDa protein (Hsc70). In addition, this protein plays a distinct but related role as a holdase that inhibits the aggregation of misfolded proteins, including the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Elevated expression of this protein has been observed in numerous human cancers. [provided by RefSeq, Mar 2017]

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 rank	MANE	Protein	UniProt
HSPH1	NM_006644.4	c.1246G>T	p.Val416Phe	missense_variant, splice_region_variant	Exon 10 of 18	ENST00000320027.10	NP_006635.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPH1	ENST00000320027.10	c.1246G>T	p.Val416Phe	missense_variant, splice_region_variant	Exon 10 of 18	1	NM_006644.4	ENSP00000318687.5
HSPH1	ENST00000602786.5	n.*774G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 9 of 17	1		ENSP00000473512.1
HSPH1	ENST00000602786.5	n.*774G>T		3_prime_UTR_variant	Exon 9 of 17	1		ENSP00000473512.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1452552 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722326

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T;.;.
Eigen	Benign	-0.059
Eigen_PC	Benign	0.034
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.50	D;D;D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.4	.;M;.;M
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-4.5	D;N;.;N
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D;D;.;D
Sift4G	Benign	0.27	T;T;T;T
Polyphen		0.30, 0.17	.;B;.;B
Vest4		0.60
MutPred		0.37		.;Loss of helix (P = 0.1299);.;Loss of helix (P = 0.1299);
MVP		0.60
MPC		0.99
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.12
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.51
dbscSNV1_RF	Benign	0.57
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

LitVar

Other links and lift over

dbSNP: rs200964846; hg19: chr13-31722228;