rs267607064

Positions:

• chr20-3228952-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_001174089.2(SLC4A11):​c.2078G>A​(p.Gly693Glu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC4A11 NM_001174089.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.37

Genes affected

SLC4A11 (HGNC:16438): (solute carrier family 4 member 11) This gene encodes a voltage-regulated, electrogenic sodium-coupled borate cotransporter that is essential for borate homeostasis, cell growth and cell proliferation. Mutations in this gene have been associated with a number of endothelial corneal dystrophies including recessive corneal endothelial dystrophy 2, corneal dystrophy and perceptive deafness, and Fuchs endothelial corneal dystrophy. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.882
• PP5: Variant 20-3228952-C-T is Pathogenic according to our data. Variant chr20-3228952-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 1320.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr20-3228952-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A11	NM_001174089.2	c.2078G>A	p.Gly693Glu	missense_variant	17/20	ENST00000642402.1	NP_001167560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1	c.2078G>A	p.Gly693Glu	missense_variant	17/20		NM_001174089.2	ENSP00000493503	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Corneal dystrophy, Fuchs endothelial, 4 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;.;.;.;.;.;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.95	D;D;.;D;D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.88	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Uncertain	2.9	M;.;.;.;.;.;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.5	N;N;.;.;.;.;N
REVEL	Pathogenic	0.70
Sift	Benign	0.063	T;D;.;.;.;.;T
Sift4G	Benign	0.063	T;T;.;.;.;.;T
Polyphen		1.0	D;.;.;.;.;.;.
Vest4		0.88
MutPred		0.85		Gain of glycosylation at S711 (P = 0.0953);.;.;.;.;.;.;
MVP		0.95
MPC		1.1
ClinPred		0.97	D
GERP RS		4.1
Varity_R		0.20
gMVP		0.96

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

LitVar

Other links and lift over

dbSNP: rs267607064; hg19: chr20-3209598;