20-3233935-C-A

Variant names:

• chr20-3233935-C-A
• rs3803956
• NM_001174089.2:c.591G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001174089.2(SLC4A11):​c.591G>T​(p.Ser197Ser) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S197S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC4A11 NM_001174089.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 24 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: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• congenital hereditary endothelial dystrophy of cornea

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

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174089.2. 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
	SLC4A11	NM_001174089.2	MANE Select	c.591G>T	p.Ser197Ser	synonymous	Exon 6 of 20	NP_001167560.1	Q8NBS3-3
	SLC4A11	NM_001174090.2		c.720G>T	p.Ser240Ser	synonymous	Exon 6 of 20	NP_001167561.1	Q8NBS3-4
	SLC4A11	NM_032034.4		c.639G>T	p.Ser213Ser	synonymous	Exon 5 of 19	NP_114423.1	Q8NBS3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A11	ENST00000642402.1	MANE Select	c.591G>T	p.Ser197Ser	synonymous	Exon 6 of 20	ENSP00000493503.1	Q8NBS3-3
	SLC4A11	ENST00000380056.7	TSL:1	c.639G>T	p.Ser213Ser	synonymous	Exon 5 of 19	ENSP00000369396.3	Q8NBS3-1
	SLC4A11	ENST00000380059.7	TSL:2	c.720G>T	p.Ser240Ser	synonymous	Exon 6 of 20	ENSP00000369399.3	Q8NBS3-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.11
DANN	Benign	0.36
PhyloP100		-1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3803956; hg19: chr20-3214581;