NM_004174.4:c.1145G>C

Variant names:

• chr5-483270-C-G
• NM_004174.4:c.1145G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004174.4(SLC9A3):​c.1145G>C​(p.Arg382Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,392,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SLC9A3 NM_004174.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.71

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.929

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A3	NM_004174.4	c.1145G>C	p.Arg382Pro	missense_variant	Exon 6 of 17	ENST00000264938.8	NP_004165.2
SLC9A3	NM_001284351.3	c.1145G>C	p.Arg382Pro	missense_variant	Exon 6 of 17		NP_001271280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A3	ENST00000264938.8	c.1145G>C	p.Arg382Pro	missense_variant	Exon 6 of 17	1	NM_004174.4	ENSP00000264938.3
SLC9A3	ENST00000514375.1	c.1145G>C	p.Arg382Pro	missense_variant	Exon 6 of 17	1		ENSP00000422983.1
SLC9A3	ENST00000644203.1	c.1145G>C	p.Arg382Pro	missense_variant	Exon 6 of 16			ENSP00000495903.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1392584 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 684938

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000208

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	.;T;.
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Pathogenic	3.7	.;H;H
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-6.2	.;D;D
REVEL	Pathogenic	0.67
Sift	Pathogenic	0.0	.;D;D
Sift4G	Uncertain	0.0080	.;D;D
Polyphen		1.0	.;D;.
Vest4		0.95, 0.95
MutPred		0.77		Loss of MoRF binding (P = 0.0198);Loss of MoRF binding (P = 0.0198);Loss of MoRF binding (P = 0.0198);
MVP		0.83
MPC		2.3
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.97
gMVP		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-483385;