10-116727589-T-C

Variant names:

• chr10-116727589-T-C
• rs1665650
• NM_025015.3:c.40+14841A>G

Variant summary

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

The NM_025015.3(HSPA12A):​c.40+14841A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,002 control chromosomes in the GnomAD database, including 36,910 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 0.69 (36910 hom., cov: 31)
• Consequence: HSPA12A NM_025015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 33 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA12A	NM_025015.3	c.40+14841A>G		intron_variant	Intron 1 of 11	ENST00000369209.8	NP_079291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA12A	ENST00000369209.8	c.40+14841A>G		intron_variant	Intron 1 of 11	1	NM_025015.3	ENSP00000358211.3

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105106 AN: 151884 Hom.: 36893 Cov.: 31

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.692 AC: 105169 AN: 152002 Hom.: 36910 Cov.: 31 AF XY: 0.691 AC XY: 51325 AN XY: 74278

African (AFR) AF: 0.596 AC: 24682 AN: 41436

American (AMR) AF: 0.796 AC: 12158 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2934 AN: 3470

East Asian (EAS) AF: 0.686 AC: 3543 AN: 5164

South Asian (SAS) AF: 0.765 AC: 3667 AN: 4796

European-Finnish (FIN) AF: 0.603 AC: 6366 AN: 10556

Middle Eastern (MID) AF: 0.877 AC: 256 AN: 292

European-Non Finnish (NFE) AF: 0.727 AC: 49427 AN: 68002

Other (OTH) AF: 0.737 AC: 1550 AN: 2102

Alfa AF: 0.712 Hom.: 74175

Bravo AF: 0.700

Asia WGS AF: 0.719 AC: 2501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.39
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1665650; hg19: chr10-118487100;