chr5-138567395-A-G

Variant names:

• chr5-138567395-A-G
• rs256014
• NM_004134.7:c.716+60T>C

Variant summary

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

The NM_004134.7(HSPA9):​c.716+60T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,348,552 control chromosomes in the GnomAD database, including 144,853 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 0.52 (23084 hom., cov: 32)
  • Exomes 𝑓: 0.44 (121769 hom.)
• Consequence: HSPA9 NM_004134.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258

Genes affected

HSPA9 (HGNC:5244): (heat shock protein family A (Hsp70) member 9) This gene encodes a member of the heat shock protein 70 gene family. The encoded protein is primarily localized to the mitochondria but is also found in the endoplasmic reticulum, plasma membrane and cytoplasmic vesicles. This protein is a heat-shock cognate protein. This protein plays a role in cell proliferation, stress response and maintenance of the mitochondria. A pseudogene of this gene is found on chromosome 2.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA9	NM_004134.7	c.716+60T>C		intron_variant	Intron 7 of 16	ENST00000297185.9	NP_004125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA9	ENST00000297185.9	c.716+60T>C		intron_variant	Intron 7 of 16	1	NM_004134.7	ENSP00000297185.3

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79481 AN: 151940 Hom.: 23034 Cov.: 32

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.437 AC: 522389 AN: 1196494 Hom.: 121769 Cov.: 17 AF XY: 0.443 AC XY: 269672 AN XY: 608132

Gnomad4 AFR exome AF: 0.753

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.430

Gnomad4 EAS exome AF: 0.812

Gnomad4 SAS exome AF: 0.638

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.395

Gnomad4 OTH exome AF: 0.461

GnomAD4 genome AF: 0.523 AC: 79587 AN: 152058 Hom.: 23084 Cov.: 32 AF XY: 0.526 AC XY: 39102 AN XY: 74326

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.502

Alfa AF: 0.457 Hom.: 2165

Bravo AF: 0.536

Asia WGS AF: 0.702 AC: 2442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.89
DANN	Benign	0.65

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: rs256014; hg19: chr5-137903084;