20-49878113-A-T

Variant names:

• chr20-49878113-A-T
• rs6020100
• NM_015266.3:c.1158+50A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015266.3(SLC9A8):​c.1158+50A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC9A8 NM_015266.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 6 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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.1158+50A>T		intron	N/A	NP_056081.1	Q9Y2E8-1
	SLC9A8	NM_001260491.2		c.1206+50A>T		intron	N/A	NP_001247420.1	Q9Y2E8-2
	SLC9A8	NR_048537.2		n.1218+50A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A8	ENST00000361573.3	TSL:1 MANE Select	c.1158+50A>T		intron	N/A	ENSP00000354966.2	Q9Y2E8-1
	SLC9A8	ENST00000851371.1		c.1257+50A>T		intron	N/A	ENSP00000521430.1
	SLC9A8	ENST00000417961.5	TSL:2	c.1206+50A>T		intron	N/A	ENSP00000416418.1	Q9Y2E8-2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151276 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 976318 Hom.: 0 Cov.: 12 AF XY: 0.00000199 AC XY: 1 AN XY: 501384

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21294

American (AMR) AF: 0.00 AC: 0 AN: 25982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20380

East Asian (EAS) AF: 0.00 AC: 0 AN: 34142

South Asian (SAS) AF: 0.00 AC: 0 AN: 62398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3724

European-Non Finnish (NFE) AF: 0.00000139 AC: 1 AN: 721548

Other (OTH) AF: 0.00 AC: 0 AN: 42978

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151276 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 73812

African (AFR) AF: 0.00 AC: 0 AN: 41152

American (AMR) AF: 0.00 AC: 0 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67830

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 1750

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.26

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

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

Other links and lift over

dbSNP: rs6020100; hg19: chr20-48494650;