SLC4A10 p.Pro1040Pro

Variant names:

• chr2-161965131-G-G
• ENST00000446997.6:c.

Your query was ambiguous. Multiple possible variants found:

• chr2-161965132--
• chr2-161965134-C-T
• chr2-161965134-C-A
• chr2-161965134-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001178015.2(SLC4A10):​c. variant causes a intron 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC4A10 NM_001178015.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

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: PanelApp Australia, G2P, Baylor College of Medicine Research Center

ENSG00000296511 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A10	NM_001178015.2	MANE Select	c.		intron	N/A	NP_001171486.1	Q6U841-1
	SLC4A10	NM_001354440.2		c.		intron	N/A	NP_001341369.1
	SLC4A10	NM_001354460.2		c.		intron	N/A	NP_001341389.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A10	ENST00000446997.6	TSL:1 MANE Select	c.		exon_region	Exon 23 of 27	ENSP00000393066.1	Q6U841-1
	SLC4A10	ENST00000415876.6	TSL:1	c.		exon_region	Exon 22 of 26	ENSP00000395797.2	Q6U841-2
	SLC4A10	ENST00000272716.9	TSL:5	c.		exon_region	Exon 22 of 25	ENSP00000272716.5	C9J240

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-162821641;