chr18-45625755-G-T

Position:

• chr18-45625755-G-T

Variant summary

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

The NM_007163.4(SLC14A2):​c.223G>T​(p.Asp75Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000354 in 1,413,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SLC14A2 NM_007163.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.89

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]

LOC105372093 (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=0.16773024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC14A2	NM_007163.4	c.223G>T	p.Asp75Tyr	missense_variant	3/20	ENST00000255226.11	NP_009094.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC14A2	ENST00000255226.11	c.223G>T	p.Asp75Tyr	missense_variant	3/20	1	NM_007163.4	ENSP00000255226.5
SLC14A2	ENST00000586448.5	c.223G>T	p.Asp75Tyr	missense_variant	4/21	2		ENSP00000465953.1
SLC14A2	ENST00000323329.3	n.223G>T		non_coding_transcript_exon_variant	3/11	2		ENSP00000320689.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000354 AC: 5 AN: 1413568 Hom.: 0 Cov.: 31 AF XY: 0.00000285 AC XY: 2 AN XY: 701690

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: 0.00

Gnomad4 NFE exome AF: 0.00000274

Gnomad4 OTH exome AF: 0.0000342

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 09, 2024

The c.223G>T (p.D75Y) alteration is located in exon 3 (coding exon 2) of the SLC14A2 gene. This alteration results from a G to T substitution at nucleotide position 223, causing the aspartic acid (D) at amino acid position 75 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	25
DANN	Benign	0.87
DEOGEN2	Benign	0.18	T;T
Eigen	Benign	0.021
Eigen_PC	Benign	0.094
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.30	.;N
REVEL	Benign	0.15
Sift	Uncertain	0.0070	.;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.86	P;P
Vest4		0.25
MutPred		0.27		Gain of MoRF binding (P = 0.0219);Gain of MoRF binding (P = 0.0219);
MVP		0.39
MPC		0.15
ClinPred		0.42	T
GERP RS		6.0
Varity_R		0.18
gMVP		0.30

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: rs1211258954; hg19: chr18-43205720;