chr13-113492578-C-T

Variant names:

• chr13-113492578-C-T
• rs2261120
• NM_017905.6:c.-81+1305C>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.-81+1305C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,098 control chromosomes in the GnomAD database, including 3,458 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 0.19 (3458 hom., cov: 33)
• Consequence: SLC9D1 NM_017905.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9D1	NM_017905.6	MANE Select	c.-81+1305C>T		intron	N/A	NP_060375.4
	SLC9D1	NM_001349744.2		c.-81+1305C>T		intron	N/A	NP_001336673.1
	SLC9D1	NM_001349742.2		c.-81+1305C>T		intron	N/A	NP_001336671.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCO3	ENST00000434316.7	TSL:1 MANE Select	c.-81+1305C>T		intron	N/A	ENSP00000389399.2	Q6UWJ1-1
	TMCO3	ENST00000375391.5	TSL:1	c.-81+1305C>T		intron	N/A	ENSP00000364540.1	Q6UWJ1-3
	TMCO3	ENST00000955127.1		c.-81+1305C>T		intron	N/A	ENSP00000625186.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28204 AN: 151980 Hom.: 3462 Cov.: 33

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0829

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.185 AC: 28211 AN: 152098 Hom.: 3458 Cov.: 33 AF XY: 0.181 AC XY: 13495 AN XY: 74370

African (AFR) AF: 0.349 AC: 14451 AN: 41434

American (AMR) AF: 0.150 AC: 2290 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3470

East Asian (EAS) AF: 0.147 AC: 763 AN: 5174

South Asian (SAS) AF: 0.116 AC: 561 AN: 4822

European-Finnish (FIN) AF: 0.0829 AC: 878 AN: 10586

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7893 AN: 68000

Other (OTH) AF: 0.189 AC: 399 AN: 2114

Alfa AF: 0.150 Hom.: 401

Bravo AF: 0.199

Asia WGS AF: 0.139 AC: 482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.68
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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: rs2261120; hg19: chr13-114146893;