Variant 5-138556481-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_004134.7(HSPA9):c.1933C>T(p.Leu645=) 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

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.926

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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: {Benign=1, Uncertain_significance=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/exons	MANE	Protein	UniProt
HSPA9	NM_004134.7 linkuse as main transcript	c.1933C>T	p.Leu645=	synonymous_variant	16/17	ENST00000297185.9	NP_004125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA9	ENST00000297185.9 linkuse as main transcript	c.1933C>T	p.Leu645=	synonymous_variant	16/17	1	NM_004134.7	ENSP00000297185	P1

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

78862

AN:

151902

Hom.:

22700

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.477

AC:

119856

AN:

251306

Hom.:

31311

AF XY:

0.481

AC XY:

65363

AN XY:

135828

show subpopulations

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 SAS exome

AF:

0.641

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.:

AF XY:

0.438

AC XY:

318512

AN XY:

726672

show subpopulations

Gnomad4 AFR exome

AF:

0.750

Gnomad4 AMR exome

AF:

0.392

Gnomad4 ASJ exome

AF:

0.443

Gnomad4 EAS exome

AF:

0.809

Gnomad4 SAS exome

AF:

0.637

Gnomad4 FIN exome

AF:

0.351

Gnomad4 NFE exome

AF:

0.396

Gnomad4 OTH exome

AF:

0.459

GnomAD4 genome

AF:

0.519

AC:

78965

AN:

152020

Hom.:

22747

Cov.:

AF XY:

0.521

AC XY:

38717

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.749

Gnomad4 AMR

AF:

0.428

Gnomad4 ASJ

AF:

0.444

Gnomad4 EAS

AF:

0.803

Gnomad4 SAS

AF:

0.646

Gnomad4 FIN

AF:

0.350

Gnomad4 NFE

AF:

0.400

Gnomad4 OTH

AF:

0.500

Alfa

AF:

0.432

Hom.:

21243

Bravo

AF:

0.533

Asia WGS

AF:

0.699

AC:

2433

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Aug 25, 2023

PM3, BA1, BP2, BP4 -

Even-plus syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

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

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