rs7186310

Positions:

• chr16-67271610-A-C
• chr16-67271610-A-T

Variant summary

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

The NM_004594.3(SLC9A5):​c.*400A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 205,502 control chromosomes in the GnomAD database, including 10,434 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 0.26 (9596 hom., cov: 32)
  • Exomes 𝑓: 0.12 (838 hom.)
• Consequence: SLC9A5 NM_004594.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

Genes affected

SLC9A5 (HGNC:11078): (solute carrier family 9 member A5) Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in potassium ion transmembrane transport; regulation of intracellular pH; and sodium ion import across plasma membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. Implicated in end stage renal disease. [provided by Alliance of Genome Resources, Apr 2022]

LOC124903701 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9A5	NM_004594.3	c.*400A>C		3_prime_UTR_variant	16/16	ENST00000299798.16
LOC124903701	XR_007065092.1	n.462-5499T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9A5	ENST00000299798.16	c.*400A>C		3_prime_UTR_variant	16/16	1	NM_004594.3	P1
SLC9A5	ENST00000563723.5	n.3410A>C		non_coding_transcript_exon_variant	15/15	1
SLC9A5	ENST00000564704.5	n.4037A>C		non_coding_transcript_exon_variant	16/16	1
SLC9A5	ENST00000564812.5	c.*2353A>C		3_prime_UTR_variant, NMD_transcript_variant	15/15	1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39807 AN: 151960 Hom.: 9555 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0864

Gnomad EAS AF: 0.0205

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.124 AC: 6627 AN: 53424 Hom.: 838 Cov.: 0 AF XY: 0.124 AC XY: 3452 AN XY: 27842

Gnomad4 AFR exome AF: 0.650

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.0915

Gnomad4 EAS exome AF: 0.0156

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.0957

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.262 AC: 39906 AN: 152078 Hom.: 9596 Cov.: 32 AF XY: 0.259 AC XY: 19293 AN XY: 74364

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.0864

Gnomad4 EAS AF: 0.0206

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.214

Alfa AF: 0.123 Hom.: 2208

Bravo AF: 0.275

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.43

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: rs7186310; hg19: chr16-67305513;