chr10-116729204-C-G

Variant names:

• chr10-116729204-C-G
• rs1638421
• NM_025015.3:c.40+13226G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025015.3(HSPA12A):​c.40+13226G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,050 control chromosomes in the GnomAD database, including 37,178 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 (37178 hom., cov: 32)
• Consequence: HSPA12A NM_025015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA12A	NM_025015.3	c.40+13226G>C		intron_variant	Intron 1 of 11	ENST00000369209.8	NP_079291.2
HSPA12A	NM_001330164.2	c.92-21919G>C		intron_variant	Intron 2 of 12		NP_001317093.1
HSPA12A	XM_005269673.6	c.89-21919G>C		intron_variant	Intron 2 of 12		XP_005269730.1
HSPA12A	XM_011539579.3	c.89-21919G>C		intron_variant	Intron 3 of 13		XP_011537881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA12A	ENST00000369209.8	c.40+13226G>C		intron_variant	Intron 1 of 11	1	NM_025015.3	ENSP00000358211.3

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105563 AN: 151932 Hom.: 37160 Cov.: 32

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.870

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: 0.695 AC: 105629 AN: 152050 Hom.: 37178 Cov.: 32 AF XY: 0.694 AC XY: 51534 AN XY: 74300

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.798

Gnomad4 ASJ AF: 0.846

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.737

Alfa AF: 0.605 Hom.: 1729

Bravo AF: 0.704

Asia WGS AF: 0.719 AC: 2502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.50
DANN	Benign	0.45

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: rs1638421; hg19: chr10-118488715;