rs13433386

Variant names:

• chr20-49891375-A-G
• rs13433386
• NM_015266.3:c.*3439A>G

Variant summary

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

The NM_015266.3(SLC9A8):​c.*3439A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 152,110 control chromosomes in the GnomAD database, including 149 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 0.039 (149 hom., cov: 32)
  • Exomes 𝑓: 0.016 (0 hom.)
• Consequence: SLC9A8 NM_015266.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0829 is higher than 0.05.

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.*3439A>G		3_prime_UTR	Exon 16 of 16	NP_056081.1	Q9Y2E8-1
	SLC9A8	NM_001260491.2		c.*3439A>G		3_prime_UTR	Exon 16 of 16	NP_001247420.1	Q9Y2E8-2
	SLC9A8	NR_048537.2		n.5245A>G		non_coding_transcript_exon	Exon 15 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A8	ENST00000361573.3	TSL:1 MANE Select	c.*3439A>G		3_prime_UTR	Exon 16 of 16	ENSP00000354966.2	Q9Y2E8-1
	SLC9A8	ENST00000417961.5	TSL:2	c.*3439A>G		3_prime_UTR	Exon 16 of 16	ENSP00000416418.1	Q9Y2E8-2
	SLC9A8	ENST00000851368.1		c.*3439A>G		3_prime_UTR	Exon 16 of 16	ENSP00000521427.1

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5894 AN: 151928 Hom.: 148 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.0900

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0498

GnomAD4 exome AF: 0.0156 AC: 1 AN: 64 Hom.: 0 Cov.: 0 AF XY: 0.0217 AC XY: 1 AN XY: 46

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0250 AC: 1 AN: 40

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.0388 AC: 5906 AN: 152046 Hom.: 149 Cov.: 32 AF XY: 0.0380 AC XY: 2827 AN XY: 74316

African (AFR) AF: 0.0212 AC: 881 AN: 41466

American (AMR) AF: 0.0515 AC: 786 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3470

East Asian (EAS) AF: 0.0897 AC: 463 AN: 5164

South Asian (SAS) AF: 0.0191 AC: 92 AN: 4812

European-Finnish (FIN) AF: 0.0148 AC: 157 AN: 10580

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0481 AC: 3272 AN: 67966

Other (OTH) AF: 0.0502 AC: 106 AN: 2110

Alfa AF: 0.0440 Hom.: 91

Bravo AF: 0.0415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.16
PhyloP100		-2.6
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: rs13433386; hg19: chr20-48507912;