18-45731150-G-T

Position:

• chr18-45731150-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_015865.7(SLC14A1):​c.287G>T​(p.Gly96Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC14A1 NM_015865.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.21

Genes affected

SLC14A1 (HGNC:10918): (solute carrier family 14 member 1 (Kidd blood group)) The protein encoded by this gene is a membrane transporter that mediates urea transport in erythrocytes. This gene forms the basis for the Kidd blood group system. [provided by RefSeq, Mar 2009]

(HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.962

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC14A1	NM_015865.7	c.287G>T	p.Gly96Val	missense_variant	4/10	ENST00000321925.9	NP_056949.4
LOC105372093	XR_935423.3	n.826+6316C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC14A1	ENST00000321925.9	c.287G>T	p.Gly96Val	missense_variant	4/10	1	NM_015865.7	ENSP00000318546	P1
	ENST00000589510.5	n.160+6316C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Nov 01, 2022

The c.287G>T (p.G96V) alteration is located in exon 4 (coding exon 2) of the SLC14A1 gene. This alteration results from a G to T substitution at nucleotide position 287, causing the glycine (G) at amino acid position 96 to be replaced by a valine (V). 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	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T;.;T;.;.;T;T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D;.;.;D;D;D;.
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.96	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.056	D
MutationAssessor	Pathogenic	3.3	M;.;.;M;.;.;M;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-8.1	D;.;D;.;.;D;.;.
REVEL	Uncertain	0.61
Sift	Uncertain	0.0010	D;.;D;.;.;D;.;.
Sift4G	Uncertain	0.0030	D;D;D;D;T;D;D;D
Polyphen		1.0	D;.;D;D;.;D;D;.
Vest4		0.98
MutPred		0.79		Gain of helix (P = 0.0128);Gain of helix (P = 0.0128);.;Gain of helix (P = 0.0128);Gain of helix (P = 0.0128);.;Gain of helix (P = 0.0128);Gain of helix (P = 0.0128);
MVP		0.83
MPC		0.59
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.95
gMVP		0.87

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: rs2047018661; hg19: chr18-43311115;