1-153614937-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_020672.3(S100A14):​c.263T>C​(p.Ile88Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000258 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. I88S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: S100A14 NM_020672.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.37
• Publications: 2 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.4075437).

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>C	p.Ile88Thr	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>C	p.Ile88Thr	missense	Exon 4 of 4	ENSP00000340463.2	Q9HCY8
	S100A14	ENST00000476873.5	TSL:1	c.263T>C	p.Ile88Thr	missense	Exon 3 of 3	ENSP00000420296.1	Q9HCY8
	S100A14	ENST00000368701.5	TSL:2	c.263T>C	p.Ile88Thr	missense	Exon 4 of 4	ENSP00000357690.1	Q9HCY8

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000139 AC: 35 AN: 251282 AF XY: 0.000132

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000262 AC: 383 AN: 1461736 Hom.: 0 Cov.: 33 AF XY: 0.000253 AC XY: 184 AN XY: 727154

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000297 AC: 330 AN: 1111982

Other (OTH) AF: 0.000447 AC: 27 AN: 60392

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74412

African (AFR) AF: 0.0000482 AC: 2 AN: 41526

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000211 Hom.: 0

Bravo AF: 0.000162

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000181 AC: 22

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.012	D
Polyphen		0.98	D
Vest4		0.64
MVP		0.36
MPC		0.28
ClinPred		0.41	T
GERP RS		4.9
Varity_R		0.65
gMVP		0.53
Mutation Taster		=49/51	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;