NM_020672.3:c.199A>G

Variant names:

• chr1-153615001-T-C
• NM_020672.3:c.199A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020672.3(S100A14):​c.199A>G​(p.Lys67Glu) 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: S100A14 NM_020672.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18555447).

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.199A>G	p.Lys67Glu	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.199A>G	p.Lys67Glu	missense	Exon 4 of 4	ENSP00000340463.2	Q9HCY8
	S100A14	ENST00000476873.5	TSL:1	c.199A>G	p.Lys67Glu	missense	Exon 3 of 3	ENSP00000420296.1	Q9HCY8
	S100A14	ENST00000368701.5	TSL:2	c.199A>G	p.Lys67Glu	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	Benign	0.19
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T
Eigen	Benign	0.035
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.1
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.044
Sift	Benign	0.093	T
Sift4G	Uncertain	0.026	D
Polyphen		0.14	B
Vest4		0.43
MutPred		0.43		Loss of ubiquitination at K67 (P = 0.0141)
MVP		0.25
MPC		0.083
ClinPred		0.61	D
GERP RS		4.9
Varity_R		0.37
gMVP		0.59
Mutation Taster		=56/44	polymorphism

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

hg19: chr1-153587477;