rs1062840

Positions:

• chr20-49888929-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015266.3(SLC9A8):​c.*993C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,596 control chromosomes in the GnomAD database, including 1,050 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 0.11 (1049 hom., cov: 32)
  • Exomes 𝑓: 0.098 (1 hom.)
• Consequence: SLC9A8 NM_015266.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A8	NM_015266.3	c.*993C>T		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.*993C>T		3_prime_UTR_variant	16/16	1	NM_015266.3	ENSP00000354966	P1
SLC9A8	ENST00000417961.5	c.*993C>T		3_prime_UTR_variant	16/16	2		ENSP00000416418
SLC9A8	ENST00000490250.1	n.1629C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16844 AN: 152142 Hom.: 1049 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0878

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0504

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0903

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.0982 AC: 33 AN: 336 Hom.: 1 Cov.: 0 AF XY: 0.0848 AC XY: 19 AN XY: 224

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0750

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.111 AC: 16865 AN: 152260 Hom.: 1049 Cov.: 32 AF XY: 0.106 AC XY: 7925 AN XY: 74472

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.0880

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.0744

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0504

Gnomad4 NFE AF: 0.0903

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0944 Hom.: 678

Bravo AF: 0.117

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1062840; hg19: chr20-48505466;