20-49878113-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015266.3(SLC9A8):​c.1158+50A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 976,318 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: SLC9A8 NM_015266.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A8	NM_015266.3	c.1158+50A>C		intron_variant	Intron 12 of 15	ENST00000361573.3	NP_056081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A8	ENST00000361573.3	c.1158+50A>C		intron_variant	Intron 12 of 15	1	NM_015266.3	ENSP00000354966.2
SLC9A8	ENST00000417961.5	c.1206+50A>C		intron_variant	Intron 12 of 15	2		ENSP00000416418.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 976318 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 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 Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.61
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

Other links and lift over

dbSNP: rs6020100; hg19: chr20-48494650;