chr5-138556533-G-A

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

2

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]

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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
HSPA9NM_004134.7 linkuse as main transcriptc.1881C>T p.Ser627= synonymous_variant 16/17 ENST00000297185.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HSPA9ENST00000297185.9 linkuse as main transcriptc.1881C>T p.Ser627= synonymous_variant 16/171 NM_004134.7 P1

Frequencies

GnomAD3 genomes
AF:
0.00135
AC:
205
AN:
152040
Hom.:
0
Cov.:
32
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.:
1
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.:
6
Cov.:
33
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.:
0
Cov.:
32
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.:
0
Bravo
AF:
0.00176
Asia WGS
AF:
0.00260
AC:
9
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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
CADD
Benign
12
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.

Other links and lift over

dbSNP: rs1042686; hg19: chr5-137892222; COSMIC: COSV51864868; COSMIC: COSV51864868; API