Genetic Variant SLC4A10:p.Ser61Ile (chr2-161804500-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001178015.2(SLC4A10):c.182G>T(p.Ser61Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S61T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC4A10
NM_001178015.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.27

Publications

0 publications found

Variant links:

Genes affected

SLC4A10 (HGNC:13811): (solute carrier family 4 member 10) This gene belongs to a small family of sodium-coupled bicarbonate transporters (NCBTs) that regulate the intracellular pH of neurons, the secretion of bicarbonate ions across the choroid plexus, and the pH of the brain extracellular fluid. The protein encoded by this gene was initially identified as a sodium-driven chloride bicarbonate exchanger (NCBE) though there is now evidence that its sodium/bicarbonate cotransport activity is independent of any chloride ion countertransport under physiological conditions. This gene is now classified as a member A10 of the SLC4 family of transmembrane solute carriers. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]

SLC4A10 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: STRONG Submitted by: ClinGen
neurodevelopmental disorder with hypotonia and characteristic brain abnormalities
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Baylor College of Medicine Research Center, PanelApp Australia, G2P

SLC4A10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001178015.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC4A10	NM_001178015.2	MANE Select	c.182G>T	p.Ser61Ile	missense	Exon 3 of 27	NP_001171486.1	Q6U841-1
SLC4A10	NM_001354440.2		c.182G>T	p.Ser61Ile	missense	Exon 3 of 26	NP_001341369.1
SLC4A10	NM_001354460.2		c.218G>T	p.Ser73Ile	missense	Exon 4 of 28	NP_001341389.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC4A10	ENST00000446997.6	TSL:1 MANE Select	c.182G>T	p.Ser61Ile	missense	Exon 3 of 27	ENSP00000393066.1	Q6U841-1
SLC4A10	ENST00000415876.6	TSL:1	c.182G>T	p.Ser61Ile	missense	Exon 3 of 26	ENSP00000395797.2	Q6U841-2
SLC4A10	ENST00000461456.5	TSL:1	n.419G>T		non_coding_transcript_exon	Exon 4 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.079

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.23

MetaRNN

Uncertain

0.51

MetaSVM

Uncertain

0.35

MutationAssessor

Pathogenic

3.0

PhyloP100

7.3

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.48

Sift

Benign

0.14

Sift4G

Benign

0.075

Polyphen

0.97

Vest4

0.60

MutPred

0.29

Loss of phosphorylation at S61 (P = 0.0032)

MVP

0.93

MPC

1.4

ClinPred

1.0

GERP RS

5.4

Varity_R

0.59

gMVP

0.62

Mutation Taster

=41/59

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over