rs2260722

Variant names:

• chr13-113533976-A-G
• rs2260722
• NM_017905.6:c.1344-69A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-113533976-A-G
• chr13-113533976-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 14 publications found

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

ACMG classification

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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.: 33

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

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

GnomAD4 genome AF: 0.396 AC: 60175 AN: 152146 Hom.: 13815 Cov.: 33 AF XY: 0.391 AC XY: 29121 AN XY: 74388

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

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
DANN	Benign	0.60
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2260722; hg19: chr13-114188291; COSMIC: COSV64807153; COSMIC: COSV64807153;