chr20-3228952-C-T

Variant names:

• chr20-3228952-C-T
• rs267607064
• NM_001174089.2:c.2078G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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). Synonymous variant affecting the same amino acid position (i.e. G693G) has been classified as Likely benign.

• 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
• Publications: 15 publications found

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]

SLC4A11 Gene-Disease associations (from GenCC):

• corneal dystrophy, Fuchs endothelial, 4

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• congenital hereditary endothelial dystrophy of cornea

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• corneal dystrophy-perceptive deafness syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
• Fuchs' endothelial dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 1320.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A11	NM_001174089.2	c.2078G>A	p.Gly693Glu	missense_variant	Exon 17 of 20	ENST00000642402.1	NP_001167560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1	c.2078G>A	p.Gly693Glu	missense_variant	Exon 17 of 20		NM_001174089.2	ENSP00000493503.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 32

Alfa AF: 0.00332 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Corneal dystrophy, Fuchs endothelial, 4 Pathogenic:1

Jul 01, 2006

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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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;.;.;.;.;.;.
PhyloP100		3.4
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
Mutation Taster		=32/68	disease causing (ClinVar)

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: rs267607064; hg19: chr20-3209598;