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GeneBe

5-138556481-G-A

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

2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.926 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
HSPA9NM_004134.7 linkuse as main transcriptc.1933C>T p.Leu645= synonymous_variant 16/17 ENST00000297185.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HSPA9ENST00000297185.9 linkuse as main transcriptc.1933C>T p.Leu645= synonymous_variant 16/171 NM_004134.7 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.519
AC:
78862
AN:
151902
Hom.:
22700
Cov.:
32
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.:
42
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.519
AC:
78965
AN:
152020
Hom.:
22747
Cov.:
32
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 submitterclinical testingGreenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic CenterAug 25, 2023PM3, BA1, BP2, BP4 -
Even-plus syndrome Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabAug 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.

Other links and lift over

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