18-45666191-G-C

Variant names:

• chr18-45666191-G-C
• rs9960464
• NM_007163.4:c.1529G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007163.4(SLC14A2):​c.1529G>C​(p.Arg510Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC14A2 NM_007163.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755
• Publications: 0 publications found

Genes affected

SLC14A2 (HGNC:10919): (solute carrier family 14 member 2) The protein encoded by this gene belongs to the urea transporter family. In mammalian cells, urea is the chief end product of nitrogen catabolism, and plays an important role in the urinary concentration mechanism. This protein is expressed in the inner medulla of the kidney, and mediates rapid transepithelial urea transport across the inner medullary collecting duct. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2011]

ENSG00000287943 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028582782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC14A2	NM_007163.4	c.1529G>C	p.Arg510Pro	missense_variant	Exon 12 of 20	ENST00000255226.11	NP_009094.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC14A2	ENST00000255226.11	c.1529G>C	p.Arg510Pro	missense_variant	Exon 12 of 20	1	NM_007163.4	ENSP00000255226.5
SLC14A2	ENST00000586448.5	c.1529G>C	p.Arg510Pro	missense_variant	Exon 13 of 21	2		ENSP00000465953.1
ENSG00000287943	ENST00000729208.1	n.228+22558C>G		intron_variant	Intron 1 of 2
ENSG00000287943	ENST00000729209.1	n.228+22558C>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461306 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726984

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111478

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.44
DANN	Benign	0.83
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.0	.;.
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.029	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N;N
PhyloP100		-0.76
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.0	.;N
REVEL	Benign	0.0
Sift	Pathogenic	0.0	.;T
Sift4G	Benign	0.26	T;T
Vest4		0.092
ClinPred		0.091	T
GERP RS		-12
Varity_R		0.094
gMVP		0.50
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9960464; hg19: chr18-43246156;