13-113495826-T-C

Variant names:

• chr13-113495826-T-C
• NM_017905.6:c.245T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_017905.6(SLC9D1):​c.245T>C​(p.Val82Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC9D1 NM_017905.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.362
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.019929737).
• BP6: Variant 13-113495826-T-C is Benign according to our data. Variant chr13-113495826-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3178312.Status of the report is criteria_provided_single_submitter, 1 stars.

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.245T>C	p.Val82Ala	missense	Exon 2 of 13	NP_060375.4
	SLC9D1	NM_001349744.2		c.245T>C	p.Val82Ala	missense	Exon 2 of 12	NP_001336673.1
	SLC9D1	NM_001349742.2		c.245T>C	p.Val82Ala	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.245T>C	p.Val82Ala	missense	Exon 2 of 13	ENSP00000389399.2	Q6UWJ1-1
	TMCO3	ENST00000375391.5	TSL:1	c.245T>C	p.Val82Ala	missense	Exon 2 of 8	ENSP00000364540.1	Q6UWJ1-3
	TMCO3	ENST00000955127.1		c.245T>C	p.Val82Ala	missense	Exon 2 of 14	ENSP00000625186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.058
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.36
DANN	Benign	0.34
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-0.36
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.0080
Sift	Benign	0.82	T
Sift4G	Benign	0.83	T
Polyphen		0.0	B
Vest4		0.031
MutPred		0.23		Gain of catalytic residue at D81 (P = 0.0292)
MVP		0.014
MPC		0.29
ClinPred		0.021	T
GERP RS		0.41
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.013
gMVP		0.072
Mutation Taster		=97/3	polymorphism

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

hg19: chr13-114150141;