20-49815114-GTG-CTT

Variant names:

• chr20-49815114-GTG-CTT
• NM_015266.3:c.133_135delGTGinsCTT
• SLC9A8 p.Val45Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_015266.3(SLC9A8):​c.133_135delGTGinsCTT​(p.Val45Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. V45M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC9A8 NM_015266.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.83
• Publications: 0 publications found

Genes affected

SLC9A8 (HGNC:20728): (solute carrier family 9 member A8) Sodium-hydrogen exchangers (NHEs), such as SLC9A8, are integral transmembrane proteins that exchange extracellular Na+ for intracellular H+. NHEs have multiple functions, including intracellular pH homeostasis, cell volume regulation, and electroneutral NaCl absorption in epithelia (Xu et al., 2008 [PubMed 18209477]).[supplied by OMIM, Apr 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• 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_015266.3. 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
	SLC9A8	NM_015266.3	MANE Select	c.133_135delGTGinsCTT	p.Val45Leu	missense	N/A	NP_056081.1	Q9Y2E8-1
	SLC9A8	NM_001260491.2		c.133_135delGTGinsCTT	p.Val45Leu	missense	N/A	NP_001247420.1	Q9Y2E8-2
	SLC9A8	NR_048537.2		n.228_230delGTGinsCTT		non_coding_transcript_exon	Exon 2 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A8	ENST00000361573.3	TSL:1 MANE Select	c.133_135delGTGinsCTT	p.Val45Leu	missense	N/A	ENSP00000354966.2	Q9Y2E8-1
	SLC9A8	ENST00000851371.1		c.133_135delGTGinsCTT	p.Val45Leu	missense	N/A	ENSP00000521430.1
	SLC9A8	ENST00000417961.5	TSL:2	c.133_135delGTGinsCTT	p.Val45Leu	missense	N/A	ENSP00000416418.1	Q9Y2E8-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8

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: chr20-48431651;