Genetic Variant SLC9D1:c.1344-69A>G (chr13-113533976-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017905.6(SLC9D1):c.1344-69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,217,590 control chromosomes in the GnomAD database, including 63,354 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 13815 hom., cov: 33)

Exomes 𝑓: 0.29 ( 49539 hom. )

Consequence

SLC9D1
NM_017905.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

Publications

14 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

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	Effect	Exon Rank	Protein
SLC9D1	NM_017905.6	MANE Select	c.1344-69A>G	intron	N/A	NP_060375.4
SLC9D1	NM_001349744.2		c.1344-69A>G	intron	N/A	NP_001336673.1
SLC9D1	NM_001349742.2		c.1152-69A>G	intron	N/A	NP_001336671.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TMCO3	ENST00000434316.7	TSL:1 MANE Select	c.1344-69A>G	intron	N/A	ENSP00000389399.2
TMCO3	ENST00000375391.5	TSL:1	c.1226-15658A>G	intron	N/A	ENSP00000364540.1
TMCO3	ENST00000955127.1		c.1365-69A>G	intron	N/A	ENSP00000625186.1

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

60111

AN:

152028

Hom.:

13799

Cov.:

show subpopulations

Gnomad AFR

AF:

0.633

Gnomad AMI

AF:

0.406

Gnomad AMR

AF:

0.457

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.388

GnomAD4 exome

AF:

0.294

AC:

313454

AN:

1065444

Hom.:

49539

AF XY:

0.292

AC XY:

157369

AN XY:

538024

show subpopulations

African (AFR)

AF:

0.652

AC:

15758

AN:

24186

American (AMR)

AF:

0.536

AC:

14675

AN:

27368

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

5693

AN:

19262

East Asian (EAS)

AF:

0.294

AC:

10998

AN:

37452

South Asian (SAS)

AF:

0.320

AC:

20669

AN:

64592

European-Finnish (FIN)

AF:

0.233

AC:

11714

AN:

50374

Middle Eastern (MID)

AF:

0.355

AC:

1712

AN:

4816

European-Non Finnish (NFE)

AF:

0.275

AC:

217720

AN:

791094

Other (OTH)

AF:

0.313

AC:

14515

AN:

46300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

11219

22439

33658

44878

56097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6784

13568

20352

27136

33920

<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:

0.396

AC:

60175

AN:

152146

Hom.:

13815

Cov.:

AF XY:

0.391

AC XY:

29121

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.632

AC:

26244

AN:

41494

American (AMR)

AF:

0.458

AC:

6996

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

1001

AN:

3470

East Asian (EAS)

AF:

0.312

AC:

1617

AN:

5186

South Asian (SAS)

AF:

0.330

AC:

1594

AN:

4824

European-Finnish (FIN)

AF:

0.231

AC:

2448

AN:

10576

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.279

AC:

18959

AN:

67990

Other (OTH)

AF:

0.388

AC:

822

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1706

3412

5117

6823

8529

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

550

1100

1650

2200

2750

<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:

0.315

Hom.:

32213

Bravo

AF:

0.424

Asia WGS

AF:

0.350

AC:

1219

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.2

(source)

DANN

Benign

0.60

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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