rs10117

Variant names:

• chr5-138556481-G-A
• rs10117
• NM_004134.7:c.1933C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-138556481-G-A
• chr5-138556481-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_004134.7(HSPA9):​c.1933C>T​(p.Leu645Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,612,568 control chromosomes in the GnomAD database, including 167,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.52 (22747 hom., cov: 32)
  • Exomes 𝑓: 0.43 (144917 hom.)
• Consequence: HSPA9 NM_004134.7 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.926

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 5-138556481-G-A is Benign according to our data. Variant chr5-138556481-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1285357.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
• BP7: Synonymous conserved (PhyloP=0.926 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA9	NM_004134.7	c.1933C>T	p.Leu645Leu	synonymous_variant	Exon 16 of 17	ENST00000297185.9	NP_004125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA9	ENST00000297185.9	c.1933C>T	p.Leu645Leu	synonymous_variant	Exon 16 of 17	1	NM_004134.7	ENSP00000297185.3

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78862 AN: 151902 Hom.: 22700 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.498

GnomAD2 exomes AF: 0.477 AC: 119856 AN: 251306 AF XY: 0.481

Gnomad AFR exome AF: 0.750

Gnomad AMR exome AF: 0.383

Gnomad ASJ exome AF: 0.439

Gnomad EAS exome AF: 0.783

Gnomad FIN exome AF: 0.353

Gnomad NFE exome AF: 0.401

Gnomad OTH exome AF: 0.443

GnomAD4 exome AF: 0.432 AC: 631084 AN: 1460548 Hom.: 144917 Cov.: 42 AF XY: 0.438 AC XY: 318512 AN XY: 726672

Gnomad4 AFR exome AF: 0.750 AC: 25114 AN: 33468

Gnomad4 AMR exome AF: 0.392 AC: 17526 AN: 44688

Gnomad4 ASJ exome AF: 0.443 AC: 11565 AN: 26128

Gnomad4 EAS exome AF: 0.809 AC: 32121 AN: 39690

Gnomad4 SAS exome AF: 0.637 AC: 54938 AN: 86228

Gnomad4 FIN exome AF: 0.351 AC: 18662 AN: 53242

Gnomad4 NFE exome AF: 0.396 AC: 440282 AN: 1111014

Gnomad4 Remaining exome AF: 0.459 AC: 27731 AN: 60354

GnomAD4 genome AF: 0.519 AC: 78965 AN: 152020 Hom.: 22747 Cov.: 32 AF XY: 0.521 AC XY: 38717 AN XY: 74304

Gnomad4 AFR AF: 0.749 AC: 0.748505 AN: 0.748505

Gnomad4 AMR AF: 0.428 AC: 0.427767 AN: 0.427767

Gnomad4 ASJ AF: 0.444 AC: 0.444316 AN: 0.444316

Gnomad4 EAS AF: 0.803 AC: 0.802515 AN: 0.802515

Gnomad4 SAS AF: 0.646 AC: 0.645911 AN: 0.645911

Gnomad4 FIN AF: 0.350 AC: 0.349981 AN: 0.349981

Gnomad4 NFE AF: 0.400 AC: 0.399965 AN: 0.399965

Gnomad4 OTH AF: 0.500 AC: 0.500474 AN: 0.500474

Alfa AF: 0.440 Hom.: 27086

Bravo AF: 0.533

Asia WGS AF: 0.699 AC: 2433 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1

Aug 25, 2023

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PM3, BA1, BP2, BP4 -

Even-plus syndrome Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.81
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

Publications

LitVar

Other links and lift over

dbSNP: rs10117; hg19: chr5-137892170; COSMIC: COSV51864505; COSMIC: COSV51864505;