Variant chr5-138556533-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_004134.7(HSPA9):c.1881C>T(p.Ser627=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000907 in 1,613,842 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00086 ( 6 hom. )

Consequence

HSPA9
NM_004134.7 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0930

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 5-138556533-G-A is Benign according to our data. Variant chr5-138556533-G-A is described in ClinVar as [Benign]. Clinvar id is 788988.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.093 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00135 (205/152156) while in subpopulation EAS AF= 0.00405 (21/5180). AF 95% confidence interval is 0.00272. There are 0 homozygotes in gnomad4. There are 107 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 205 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA9	NM_004134.7 linkuse as main transcript	c.1881C>T	p.Ser627=	synonymous_variant	16/17	ENST00000297185.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA9	ENST00000297185.9 linkuse as main transcript	c.1881C>T	p.Ser627=	synonymous_variant	16/17	1	NM_004134.7	P1

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

205

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00137

AC:

344

AN:

250960

Hom.:

AF XY:

0.00124

AC XY:

168

AN XY:

135608

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00745

Gnomad EAS exome

AF:

0.00506

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000644

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000861

AC:

1259

AN:

1461686

Hom.:

Cov.:

AF XY:

0.000849

AC XY:

617

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00248

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.00624

Gnomad4 EAS exome

AF:

0.00925

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000377

Gnomad4 OTH exome

AF:

0.00194

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

152156

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00234

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00405

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.00176

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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