NM_015266.3:c.1638+26T>C

Variant names:

• chr20-49886924-T-C
• rs7270636
• NM_015266.3:c.1638+26T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015266.3(SLC9A8):​c.1638+26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0774 in 1,602,330 control chromosomes in the GnomAD database, including 5,293 homozygotes. 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 0.098 (897 hom., cov: 32)
  • Exomes 𝑓: 0.075 (4396 hom.)
• Consequence: SLC9A8 NM_015266.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A8	NM_015266.3	c.1638+26T>C		intron_variant	Intron 15 of 15	ENST00000361573.3	NP_056081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A8	ENST00000361573.3	c.1638+26T>C		intron_variant	Intron 15 of 15	1	NM_015266.3	ENSP00000354966.2
SLC9A8	ENST00000417961.5	c.1686+26T>C		intron_variant	Intron 15 of 15	2		ENSP00000416418.1
SLC9A8	ENST00000490250.1	n.528+26T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0977 AC: 14854 AN: 152074 Hom.: 890 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0403

Gnomad SAS AF: 0.0799

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0729

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.0816 AC: 19824 AN: 242978 AF XY: 0.0803

Gnomad AFR exome AF: 0.162

Gnomad AMR exome AF: 0.0738

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.0373

Gnomad FIN exome AF: 0.0753

Gnomad NFE exome AF: 0.0751

Gnomad OTH exome AF: 0.0841

GnomAD4 exome AF: 0.0753 AC: 109150 AN: 1450138 Hom.: 4396 Cov.: 31 AF XY: 0.0757 AC XY: 54507 AN XY: 719996

African (AFR) AF: 0.166 AC: 5521 AN: 33292

American (AMR) AF: 0.0744 AC: 3273 AN: 44006

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3496 AN: 25462

East Asian (EAS) AF: 0.0413 AC: 1624 AN: 39338

South Asian (SAS) AF: 0.0822 AC: 6981 AN: 84914

European-Finnish (FIN) AF: 0.0755 AC: 4000 AN: 53000

Middle Eastern (MID) AF: 0.109 AC: 624 AN: 5718

European-Non Finnish (NFE) AF: 0.0716 AC: 79033 AN: 1104554

Other (OTH) AF: 0.0768 AC: 4598 AN: 59854

GnomAD4 genome AF: 0.0979 AC: 14902 AN: 152192 Hom.: 897 Cov.: 32 AF XY: 0.0959 AC XY: 7137 AN XY: 74412

African (AFR) AF: 0.162 AC: 6703 AN: 41494

American (AMR) AF: 0.0666 AC: 1019 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 487 AN: 3466

East Asian (EAS) AF: 0.0401 AC: 207 AN: 5168

South Asian (SAS) AF: 0.0804 AC: 388 AN: 4826

European-Finnish (FIN) AF: 0.0759 AC: 805 AN: 10612

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0730 AC: 4962 AN: 68014

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.0945 Hom.: 162

Bravo AF: 0.101

Asia WGS AF: 0.0630 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.41
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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: rs7270636; hg19: chr20-48503461;