21-14382665-G-T

Variant names:

• chr21-14382665-G-T
• rs1882881
• NM_006948.5:c.25+430C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006948.5(HSPA13):​c.25+430C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,700 control chromosomes in the GnomAD database, including 27,344 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (27344 hom., cov: 30)
• Consequence: HSPA13 NM_006948.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• Publications: 2 publications found

Genes affected

HSPA13 (HGNC:11375): (heat shock protein family A (Hsp70) member 13) The protein encoded by this gene is a member of the heat shock protein 70 family and is found associated with microsomes. Members of this protein family play a role in the processing of cytosolic and secretory proteins, as well as in the removal of denatured or incorrectly-folded proteins. The encoded protein contains an ATPase domain and has been shown to associate with a ubiquitin-like protein. [provided by RefSeq, Jul 2008]

ENSG00000296939 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA13	NM_006948.5	c.25+430C>A		intron_variant	Intron 1 of 4	ENST00000285667.4	NP_008879.3
LOC105369304	XR_001754959.3	n.-101G>T		upstream_gene_variant
LOC105369304	XR_007067924.1	n.-101G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA13	ENST00000285667.4	c.25+430C>A		intron_variant	Intron 1 of 4	1	NM_006948.5	ENSP00000285667.3
HSPA13	ENST00000478035.1	n.208+612C>A		intron_variant	Intron 1 of 2	3
ENSG00000296939	ENST00000743737.1	n.-61G>T		upstream_gene_variant
ENSG00000296939	ENST00000743738.1	n.-47G>T		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89639 AN: 151580 Hom.: 27350 Cov.: 30

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.602

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.591 AC: 89654 AN: 151700 Hom.: 27344 Cov.: 30 AF XY: 0.589 AC XY: 43663 AN XY: 74132

African (AFR) AF: 0.451 AC: 18631 AN: 41320

American (AMR) AF: 0.529 AC: 8073 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2426 AN: 3468

East Asian (EAS) AF: 0.510 AC: 2633 AN: 5158

South Asian (SAS) AF: 0.573 AC: 2755 AN: 4806

European-Finnish (FIN) AF: 0.645 AC: 6762 AN: 10476

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46284 AN: 67894

Other (OTH) AF: 0.602 AC: 1270 AN: 2110

Alfa AF: 0.648 Hom.: 122352

Bravo AF: 0.573

Asia WGS AF: 0.544 AC: 1893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.031
DANN	Benign	0.61
PhyloP100		-2.2
PromoterAI		0.00040	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1882881; hg19: chr21-15754986;