1-153535254-A-G

Variant summary

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

The NM_014624.4(S100A6):​c.86T>C​(p.Leu29Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

S100A6
NM_014624.4 missense

Scores

4
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.97
Variant links:
Genes affected
S100A6 (HGNC:10496): (S100 calcium binding protein A6) 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 may function in stimulation of Ca2+-dependent insulin release, stimulation of prolactin secretion, and exocytosis. Chromosomal rearrangements and altered expression of this gene have been implicated in melanoma. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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, 0.863

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
S100A6NM_014624.4 linkc.86T>C p.Leu29Pro missense_variant Exon 2 of 3 ENST00000368719.9 NP_055439.1 P06703
S100A6XM_017002033.2 linkc.86T>C p.Leu29Pro missense_variant Exon 2 of 3 XP_016857522.1 P06703
LOC124904423XR_007066630.1 linkn.831A>G non_coding_transcript_exon_variant Exon 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
S100A6ENST00000368719.9 linkc.86T>C p.Leu29Pro missense_variant Exon 2 of 3 1 NM_014624.4 ENSP00000357708.3 P06703

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251442
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461838
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.000111
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.86T>C (p.L29P) alteration is located in exon 2 (coding exon 1) of the S100A6 gene. This alteration results from a T to C substitution at nucleotide position 86, causing the leucine (L) at amino acid position 29 to be replaced by a proline (P). 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
0.95
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.13
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.38
T;T;T;T
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.90
.;.;D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.86
D;D;D;D
MetaSVM
Benign
-0.78
T
PrimateAI
Uncertain
0.53
T
PROVEAN
Pathogenic
-6.6
.;D;D;.
REVEL
Uncertain
0.49
Sift
Uncertain
0.0010
.;D;D;.
Sift4G
Benign
0.070
T;T;T;T
Polyphen
1.0
D;D;D;.
Vest4
0.88
MutPred
0.76
Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);
MVP
0.54
MPC
0.47
ClinPred
0.98
D
GERP RS
3.7
Varity_R
0.98
gMVP
0.95

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: rs1257177646; hg19: chr1-153507730; COSMIC: COSV63297223; COSMIC: COSV63297223; API