1-151986178-T-G

Position:

• chr1-151986178-T-G

Variant summary

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

The ENST00000368811.8(S100A10):​c.53A>C​(p.Lys18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: S100A10 ENST00000368811.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.593

Genes affected

S100A10 (HGNC:10487): (S100 calcium binding protein A10) 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 exocytosis and endocytosis. [provided by RefSeq, Jul 2008]

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=0.18193579).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S100A10	NM_002966.3	c.53A>C	p.Lys18Thr	missense_variant	2/3	ENST00000368811.8	NP_002957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S100A10	ENST00000368811.8	c.53A>C	p.Lys18Thr	missense_variant	2/3	1	NM_002966.3	ENSP00000357801	P1
S100A10	ENST00000368809.1	c.53A>C	p.Lys18Thr	missense_variant	2/3	3		ENSP00000357799	P1
S100A10	ENST00000478348.1	n.152A>C		non_coding_transcript_exon_variant	2/3	3
S100A10	ENST00000478574.5	n.147A>C		non_coding_transcript_exon_variant	2/4	3

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2022

The c.53A>C (p.K18T) alteration is located in exon 2 (coding exon 1) of the S100A10 gene. This alteration results from a A to C substitution at nucleotide position 53, causing the lysine (K) at amino acid position 18 to be replaced by a threonine (T). 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	Uncertain	0.55
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.10	.;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.80	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.046
Sift	Benign	0.15	T;T
Sift4G	Uncertain	0.054	T;T
Polyphen		0.0060	B;B
Vest4		0.40
MVP		0.15
MPC		0.62
ClinPred		0.50	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.26
gMVP		0.73

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: chr1-151958654;