NM_014624.4:c.269G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014624.4(S100A6):c.269G>A(p.Gly90Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,606,172 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 22 hom. )

Consequence

S100A6
NM_014624.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.114

Publications

4 publications found

Variant links:

Genes affected

S100A6 (HGNC:10496): (S100 calcium binding protein A6) 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 stimulation of Ca2+-dependent insulin release, stimulation of prolactin secretion, and exocytosis. Chromosomal rearrangements and altered expression of this gene have been implicated in melanoma. [provided by RefSeq, Jul 2008]

S100A6 links:

ENSG00000238279 (HGNC:):

ENSG00000238279 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003377676).

BP6

Variant 1-153534700-C-T is Benign according to our data. Variant chr1-153534700-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 777934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0076 (1158/152300) while in subpopulation AFR AF = 0.0263 (1093/41540). AF 95% confidence interval is 0.025. There are 18 homozygotes in GnomAd4. There are 564 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014624.4. 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
	S100A6	NM_014624.4	MANE Select	c.269G>A	p.Gly90Asp	missense	Exon 3 of 3	NP_055439.1	P06703

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
S100A6	ENST00000368719.9	TSL:1 MANE Select	c.269G>A	p.Gly90Asp	missense	Exon 3 of 3	ENSP00000357708.3	P06703
S100A6	ENST00000368720.6	TSL:3	c.269G>A	p.Gly90Asp	missense	Exon 4 of 4	ENSP00000357709.1	P06703
S100A6	ENST00000496817.5	TSL:2	c.269G>A	p.Gly90Asp	missense	Exon 3 of 3	ENSP00000473589.1	P06703

Frequencies

GnomAD3 genomes

AF:

0.00749

AC:

1140

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00194

AC:

475

AN:

244870

AF XY:

0.00140

show subpopulations

Gnomad AFR exome

AF:

0.0255

Gnomad AMR exome

AF:

0.00155

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000449

Gnomad OTH exome

AF:

0.000336

GnomAD4 exome

AF:

0.000823

AC:

1196

AN:

1453872

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

515

AN XY:

723042

show subpopulations

African (AFR)

AF:

0.0286

AC:

945

AN:

33076

American (AMR)

AF:

0.00125

AC:

AN:

43098

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25670

East Asian (EAS)

AF:

0.00

AC:

AN:

39428

South Asian (SAS)

AF:

0.000247

AC:

AN:

85066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53300

Middle Eastern (MID)

AF:

0.00227

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000343

AC:

AN:

1108462

Other (OTH)

AF:

0.00208

AC:

125

AN:

60048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

109

163

218

272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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

AF:

0.00760

AC:

1158

AN:

152300

Hom.:

Cov.:

AF XY:

0.00757

AC XY:

564

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0263

AC:

1093

AN:

41540

American (AMR)

AF:

0.00301

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68028

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

130

195

260

325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00347

Hom.:

Bravo

AF:

0.00853

ESP6500AA

AF:

0.0238

AC:

105

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00239

AC:

290

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000238

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.087

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.93

PhyloP100

0.11

PrimateAI

Benign

0.34

PROVEAN

Benign

1.7

REVEL

Benign

0.14

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.078

MVP

0.31

MPC

0.67

ClinPred

0.050

GERP RS

-0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.57

gMVP

0.26

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over