18-45739554-G-T

Variant names:

• chr18-45739554-G-T
• rs1058396
• NM_015865.7:c.838G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015865.7(SLC14A1):​c.838G>T​(p.Asp280Tyr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D280N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC14A1 NM_015865.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.723
• Publications: 83 publications found

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]

ENSG00000288545 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC14A1	NM_015865.7	c.838G>T	p.Asp280Tyr	missense_variant	Exon 8 of 10	ENST00000321925.9	NP_056949.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC14A1	ENST00000321925.9	c.838G>T	p.Asp280Tyr	missense_variant	Exon 8 of 10	1	NM_015865.7	ENSP00000318546.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;.;.;T;.;.;.;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.0	.;T;.;.;.;T;T;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.5	M;.;.;.;M;.;.;.;M
PhyloP100		0.72
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.1	D;D;D;.;.;D;D;D;.
REVEL	Benign	0.21
Sift	Benign	0.041	D;D;D;.;.;D;D;D;.
Sift4G	Uncertain	0.029	D;D;D;D;.;D;D;D;D
Vest4		0.33
ClinPred		0.92	D
GERP RS		-7.6
Varity_R		0.42
gMVP		0.83
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.28		Position offset: -26

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

Other links and lift over

dbSNP: rs1058396; hg19: chr18-43319519;