10-116713204-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_025015.3(HSPA12A):c.41-5919A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 150,718 control chromosomes in the GnomAD database, including 5,656 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 0.27 (5656 hom., cov: 29)
• Consequence: HSPA12A NM_025015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA12A	NM_025015.3	c.41-5919A>G		intron_variant		ENST00000369209.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA12A	ENST00000369209.8	c.41-5919A>G		intron_variant		1	NM_025015.3	P1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40317 AN: 150610 Hom.: 5652 Cov.: 29

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.268 AC: 40340 AN: 150718 Hom.: 5656 Cov.: 29 AF XY: 0.269 AC XY: 19775 AN XY: 73534

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.236

Alfa AF: 0.225 Hom.: 5737

Bravo AF: 0.272

Asia WGS AF: 0.278 AC: 966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	20
Dann	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs4752003; hg19: chr10-118472715;