chr13-113495640-T-G

Variant names:

• chr13-113495640-T-G
• NM_017905.6:c.59T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017905.6(SLC9D1):​c.59T>G​(p.Val20Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,438,392 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC9D1 NM_017905.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.282
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08927038).

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.59T>G	p.Val20Gly	missense	Exon 2 of 13	NP_060375.4
	SLC9D1	NM_001349744.2		c.59T>G	p.Val20Gly	missense	Exon 2 of 12	NP_001336673.1
	SLC9D1	NM_001349742.2		c.59T>G	p.Val20Gly	missense	Exon 2 of 12	NP_001336671.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCO3	ENST00000434316.7	TSL:1 MANE Select	c.59T>G	p.Val20Gly	missense	Exon 2 of 13	ENSP00000389399.2	Q6UWJ1-1
	TMCO3	ENST00000375391.5	TSL:1	c.59T>G	p.Val20Gly	missense	Exon 2 of 8	ENSP00000364540.1	Q6UWJ1-3
	TMCO3	ENST00000955127.1		c.59T>G	p.Val20Gly	missense	Exon 2 of 14	ENSP00000625186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1438392 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 712066

African (AFR) AF: 0.00 AC: 0 AN: 32994

American (AMR) AF: 0.00 AC: 0 AN: 43276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24558

East Asian (EAS) AF: 0.00 AC: 0 AN: 39376

South Asian (SAS) AF: 0.00 AC: 0 AN: 83264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5650

European-Non Finnish (NFE) AF: 0.00000273 AC: 3 AN: 1097630

Other (OTH) AF: 0.00 AC: 0 AN: 59338

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.0
DANN	Benign	0.91
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.28
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.044
Sift	Benign	0.33	T
Sift4G	Uncertain	0.024	D
Polyphen		0.0	B
Vest4		0.14
MutPred		0.31		Gain of catalytic residue at L16 (P = 0)
MVP		0.030
MPC		0.32
ClinPred		0.081	T
GERP RS		-0.45
PromoterAI		0.10	Neutral
Varity_R		0.044
gMVP		0.27
Mutation Taster		=93/7	polymorphism

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

hg19: chr13-114149955;