11-123060258-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_006597.6(HSPA8):c.422A>G(p.Asn141Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
HSPA8
NM_006597.6 missense
NM_006597.6 missense
Scores
7
11
Clinical Significance
Conservation
PhyloP100: 6.16
Genes affected
HSPA8 (HGNC:5241): (heat shock protein family A (Hsp70) member 8) This gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. This protein belongs to the latter group, which are also referred to as heat-shock cognate proteins. It functions as a chaperone, and binds to nascent polypeptides to facilitate correct folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, HSPA8
BP4
?
Computational evidence support a benign effect (MetaRNN=0.29785812).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPA8 | NM_006597.6 | c.422A>G | p.Asn141Ser | missense_variant | 4/9 | ENST00000534624.6 | |
HSPA8 | NM_153201.4 | c.422A>G | p.Asn141Ser | missense_variant | 4/8 | ||
HSPA8 | XM_011542798.2 | c.422A>G | p.Asn141Ser | missense_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPA8 | ENST00000534624.6 | c.422A>G | p.Asn141Ser | missense_variant | 4/9 | 1 | NM_006597.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152076Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250836Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135712
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461194Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 726972
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 29, 2022 | The c.422A>G (p.N141S) alteration is located in exon 4 (coding exon 3) of the HSPA8 gene. This alteration results from a A to G substitution at nucleotide position 422, causing the asparagine (N) at amino acid position 141 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.;T;T;T;T;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N;N;N;D;D;D;D;D
REVEL
Benign
Sift
Benign
T;T;.;T;T;T;T;T;T;T
Sift4G
Uncertain
T;T;T;T;.;.;.;.;T;.
Polyphen
B;B;P;B;.;.;.;.;.;.
Vest4
MutPred
Gain of glycosylation at N141 (P = 0.0703);Gain of glycosylation at N141 (P = 0.0703);Gain of glycosylation at N141 (P = 0.0703);Gain of glycosylation at N141 (P = 0.0703);.;.;Gain of glycosylation at N141 (P = 0.0703);Gain of glycosylation at N141 (P = 0.0703);Gain of glycosylation at N141 (P = 0.0703);Gain of glycosylation at N141 (P = 0.0703);
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at