20-49891375-A-G

Position:

• chr20-49891375-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A8	NM_015266.3	c.*3439A>G		3_prime_UTR_variant	16/16	ENST00000361573.3	NP_056081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A8	ENST00000361573.3	c.*3439A>G		3_prime_UTR_variant	16/16	1	NM_015266.3	ENSP00000354966	P1
SLC9A8	ENST00000417961.5	c.*3439A>G		3_prime_UTR_variant	16/16	2		ENSP00000416418
SLC9A8	ENST00000490250.1	n.4075A>G		non_coding_transcript_exon_variant	2/2	2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0250

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.0212

Gnomad4 AMR AF: 0.0515

Gnomad4 ASJ AF: 0.0331

Gnomad4 EAS AF: 0.0897

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.0148

Gnomad4 NFE AF: 0.0481

Gnomad4 OTH AF: 0.0502

Alfa AF: 0.0432 Hom.: 58

Bravo AF: 0.0415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs13433386; hg19: chr20-48507912;