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GeneBe

1-153537384-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001394232.1(S100A5):c.191A>T(p.Asp64Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D64N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

S100A5
NM_001394232.1 missense

Scores

5
10
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.38
Variant links:
Genes affected
S100A5 (HGNC:10495): (S100 calcium binding protein A5) The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein has a Ca2+ affinity 20- to 100-fold higher than the other S100 proteins studied under identical conditions. This protein also binds Zn2+ and Cu2+, and Cu2+ strongly which impairs the binding of Ca2+. This protein is expressed in very restricted regions of the adult brain. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.934

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100A5NM_001394232.1 linkuse as main transcriptc.191A>T p.Asp64Val missense_variant 3/3 ENST00000368717.3
LOC124904423XR_007066630.1 linkuse as main transcriptn.2961T>A non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100A5ENST00000368717.3 linkuse as main transcriptc.191A>T p.Asp64Val missense_variant 3/33 NM_001394232.1 P1P33763-1
S100A5ENST00000368718.5 linkuse as main transcriptc.191A>T p.Asp64Val missense_variant 4/41 P1P33763-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMar 16, 2022The c.191A>T (p.D64V) alteration is located in exon 4 (coding exon 2) of the S100A5 gene. This alteration results from a A to T substitution at nucleotide position 191, causing the aspartic acid (D) at amino acid position 64 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
Cadd
Uncertain
25
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.50
T;T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.95
D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.93
D;D
MetaSVM
Benign
-0.97
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.57
T
PROVEAN
Pathogenic
-8.6
D;D
REVEL
Uncertain
0.46
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Vest4
0.90
MutPred
0.73
Loss of disorder (P = 0.0351);Loss of disorder (P = 0.0351);
MVP
0.62
MPC
0.065
ClinPred
0.99
D
GERP RS
4.4
Varity_R
0.88
gMVP
0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-153509860; API