rs146547322

Positions:

• chr5-476619-C-A
• chr5-476619-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004174.4(SLC9A3):​c.1814G>T​(p.Arg605Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC9A3 NM_004174.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52

Genes affected

SLC9A3 (HGNC:11073): (solute carrier family 9 member A3) The protein encoded by this gene is an epithelial brush border Na/H exchanger that uses an inward sodium ion gradient to expel acids from the cell. Defects in this gene are a cause of congenital secretory sodium diarrhea. Pseudogenes of this gene exist on chromosomes 10 and 22. [provided by RefSeq, Mar 2016]

SLC9A3-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14785123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A3	NM_004174.4	c.1814G>T	p.Arg605Leu	missense_variant	12/17	ENST00000264938.8	NP_004165.2
SLC9A3	NM_001284351.3	c.1787G>T	p.Arg596Leu	missense_variant	12/17		NP_001271280.1
SLC9A3-AS1	NR_125375.1	n.679+56C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A3	ENST00000264938.8	c.1814G>T	p.Arg605Leu	missense_variant	12/17	1	NM_004174.4	ENSP00000264938.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 246780 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134110

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Benign	0.77
DEOGEN2	Benign	0.062	.;T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.85	D;D;D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.8	.;L;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.24	.;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.40	.;T;T
Sift4G	Benign	0.74	.;T;T
Polyphen		0.49	.;P;.
Vest4		0.61, 0.59
MutPred		0.37		Loss of disorder (P = 0.0488);Loss of disorder (P = 0.0488);.;
MVP		0.73
MPC		0.52
ClinPred		0.70	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.16
gMVP		0.40

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: rs146547322; hg19: chr5-476734;