1-153614937-A-C

Variant names:

• chr1-153614937-A-C
• rs142669194
• NM_020672.3:c.263T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020672.3(S100A14):​c.263T>G​(p.Ile88Ser) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: S100A14 NM_020672.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.37
• Publications: 0 publications found

Genes affected

S100A14 (HGNC:18901): (S100 calcium binding protein A14) This gene encodes a member of the S100 protein family which contains an EF-hand motif and binds calcium. The gene is located in a cluster of S100 genes on chromosome 1. Levels of the encoded protein have been found to be lower in cancerous tissue and associated with metastasis suggesting a tumor suppressor function (PMID: 19956863, 19351828). [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020672.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A14	NM_020672.3	MANE Select	c.263T>G	p.Ile88Ser	missense	Exon 4 of 4	NP_065723.1	Q9HCY8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A14	ENST00000344616.4	TSL:1 MANE Select	c.263T>G	p.Ile88Ser	missense	Exon 4 of 4	ENSP00000340463.2	Q9HCY8
	S100A14	ENST00000476873.5	TSL:1	c.263T>G	p.Ile88Ser	missense	Exon 3 of 3	ENSP00000420296.1	Q9HCY8
	S100A14	ENST00000368701.5	TSL:2	c.263T>G	p.Ile88Ser	missense	Exon 4 of 4	ENSP00000357690.1	Q9HCY8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.78
MutPred		0.70		Gain of disorder (P = 2e-04)
MVP		0.46
MPC		0.33
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.79
gMVP		0.75
Mutation Taster		=45/55	disease causing

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

Other links and lift over

dbSNP: rs142669194; hg19: chr1-153587413;