Genetic Variant NM_017905.6:c.149T>C (chr13-113495730-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017905.6(SLC9D1):c.149T>C(p.Val50Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

SLC9D1
NM_017905.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03

Publications

0 publications found

Variant links:

Genes affected

SLC9D1 (HGNC:20329): (transmembrane and coiled-coil domains 3) This gene encodes a member of the monovalent cation:proton antiporter 2 (CPA2) family of transporter proteins. Members of this family typically couple the export of monovalent cations, such as potassium or sodium, to the import of protons across cellular membranes. Mutations in this gene have been identified in patients with a rare inherited vision defect, cornea guttata with anterior polar cataract. [provided by RefSeq, Mar 2017]

SLC9D1 Gene-Disease associations (from GenCC):

Fuchs' endothelial dystrophy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SLC9D1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016032815).

BS2

High AC in GnomAdExome4 at 56 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017905.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC9D1	NM_017905.6	MANE Select	c.149T>C	p.Val50Ala	missense	Exon 2 of 13	NP_060375.4
SLC9D1	NM_001349744.2		c.149T>C	p.Val50Ala	missense	Exon 2 of 12	NP_001336673.1
SLC9D1	NM_001349742.2		c.149T>C	p.Val50Ala	missense	Exon 2 of 12	NP_001336671.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMCO3	ENST00000434316.7	TSL:1 MANE Select	c.149T>C	p.Val50Ala	missense	Exon 2 of 13	ENSP00000389399.2	Q6UWJ1-1
TMCO3	ENST00000375391.5	TSL:1	c.149T>C	p.Val50Ala	missense	Exon 2 of 8	ENSP00000364540.1	Q6UWJ1-3
TMCO3	ENST00000955127.1		c.149T>C	p.Val50Ala	missense	Exon 2 of 14	ENSP00000625186.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000798

AC:

AN:

250626

AF XY:

0.0000590

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1461680

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00134

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1111900

Other (OTH)

AF:

0.000166

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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

AF:

0.0000263

AC:

AN:

152050

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41374

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

-0.34

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.010

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.61

M_CAP

Benign

0.0042

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.16

PhyloP100

2.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.49

REVEL

Benign

0.047

Sift

Benign

0.37

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.15

MutPred

0.33

Gain of disorder (P = 0.0407)

MVP

0.014

MPC

0.30

ClinPred

0.015

GERP RS

-1.6

PromoterAI

0.032

Neutral

(source)

Varity_R

0.016

gMVP

0.43

Mutation Taster

=86/14

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over