rs143042985

Variant names:

• chr1-153535311-C-A
• NM_014624.4:c.29G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-153535311-C-A
• chr1-153535311-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014624.4(S100A6):​c.29G>T​(p.Gly10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G10D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: S100A6 NM_014624.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950

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]

LOC124904423 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12412804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100A6	NM_014624.4	c.29G>T	p.Gly10Val	missense_variant	Exon 2 of 3	ENST00000368719.9	NP_055439.1
S100A6	XM_017002033.2	c.29G>T	p.Gly10Val	missense_variant	Exon 2 of 3		XP_016857522.1
LOC124904423	XR_007066630.1	n.888C>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S100A6	ENST00000368719.9	c.29G>T	p.Gly10Val	missense_variant	Exon 2 of 3	1	NM_014624.4	ENSP00000357708.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461818 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727208

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.071	T;T;T;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.23	.;.;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.51	.;N;N;.
REVEL	Benign	0.071
Sift	Benign	0.18	.;T;T;.
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.0060	B;B;B;.
Vest4		0.28
MutPred		0.44		Gain of catalytic residue at G10 (P = 0.0071);Gain of catalytic residue at G10 (P = 0.0071);Gain of catalytic residue at G10 (P = 0.0071);Gain of catalytic residue at G10 (P = 0.0071);
MVP		0.31
MPC		0.22
ClinPred		0.47	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-153507787;