Genetic Variant S100A14:p.Val34Leu (chr1-153615312-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020672.3(S100A14):c.100G>T(p.Val34Leu) 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 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V34M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

S100A14
NM_020672.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.11

Publications

0 publications found

Variant links:

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]

S100A14 links:

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ACMG classification

Classification was made for transcript

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=0.1381912).

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.100G>T	p.Val34Leu	missense	Exon 3 of 4	NP_065723.1	Q9HCY8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
S100A14	ENST00000344616.4	TSL:1 MANE Select	c.100G>T	p.Val34Leu	missense	Exon 3 of 4	ENSP00000340463.2	Q9HCY8
S100A14	ENST00000476873.5	TSL:1	c.100G>T	p.Val34Leu	missense	Exon 2 of 3	ENSP00000420296.1	Q9HCY8
S100A14	ENST00000368701.5	TSL:2	c.100G>T	p.Val34Leu	missense	Exon 3 of 4	ENSP00000357690.1	Q9HCY8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250938

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

AN:

1461730

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727162

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111988

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.053

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.77

M_CAP

Benign

0.0061

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.71

PhyloP100

3.1

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.95

REVEL

Benign

0.061

Sift

Benign

0.17

Sift4G

Benign

0.47

Polyphen

0.0010

Vest4

0.33

MutPred

0.25

Gain of loop (P = 0.1069)

MVP

0.11

MPC

0.073

ClinPred

0.050

GERP RS

2.0

Varity_R

0.095

gMVP

0.48

Mutation Taster

=77/23

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over