Variant chr5-138558545-TA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_004134.7(HSPA9):c.1515+7del variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,535,588 control chromosomes in the GnomAD database, including 32 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 18 hom. )

Consequence

HSPA9
NM_004134.7 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.49

Variant links:

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]

HSPA9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 5-138558545-TA-T is Benign according to our data. Variant chr5-138558545-TA-T is described in ClinVar as [Benign]. Clinvar id is 786063.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-138558545-TA-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00757 (1153/152282) while in subpopulation AFR AF= 0.0253 (1051/41542). AF 95% confidence interval is 0.024. There are 14 homozygotes in gnomad4. There are 544 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1153 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA9	NM_004134.7 linkuse as main transcript	c.1515+7del		splice_region_variant, intron_variant		ENST00000297185.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA9	ENST00000297185.9 linkuse as main transcript	c.1515+7del		splice_region_variant, intron_variant		1	NM_004134.7	P1

Frequencies

GnomAD3 genomes

AF:

0.00746

AC:

1135

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00196

AC:

492

AN:

251366

Hom.:

AF XY:

0.00131

AC XY:

178

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.0261

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000793

AC:

1097

AN:

1383306

Hom.:

Cov.:

AF XY:

0.000668

AC XY:

463

AN XY:

693032

show subpopulations

Gnomad4 AFR exome

AF:

0.0254

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.000623

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000709

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000548

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.00757

AC:

1153

AN:

152282

Hom.:

Cov.:

AF XY:

0.00730

AC XY:

544

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0253

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00434

Hom.:

Bravo

AF:

0.00893

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HSPA9-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 25, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over