18-45734300-G-C

Variant names:

• chr18-45734300-G-C
• NM_015865.7:c.368G>C

Variant summary

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

The NM_015865.7(SLC14A1):​c.368G>C​(p.Gly123Ala) 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: 9.15

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

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, 0.977

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC14A1	NM_015865.7	c.368G>C	p.Gly123Ala	missense_variant	Exon 5 of 10	ENST00000321925.9	NP_056949.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC14A1	ENST00000321925.9	c.368G>C	p.Gly123Ala	missense_variant	Exon 5 of 10	1	NM_015865.7	ENSP00000318546.4

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

Sep 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.368G>C (p.G123A) alteration is located in exon 5 (coding exon 3) of the SLC14A1 gene. This alteration results from a G to C substitution at nucleotide position 368, causing the glycine (G) at amino acid position 123 to be replaced by an alanine (A). 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	0.41
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;T;.;T;.;T;.;.;.;.;T;T
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	.;D;D;D;.;.;D;D;D;D;D;.
M_CAP	Uncertain	0.098	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Pathogenic	3.4	M;.;.;.;.;M;.;.;.;.;M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.8	D;.;.;D;D;.;D;.;D;.;.;.
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0050	D;.;.;D;D;.;D;.;D;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;.;D;D;D;D;D;D
Polyphen		1.0	D;.;.;D;D;D;.;.;D;.;D;.
Vest4		0.95
MutPred		0.91		Gain of helix (P = 0.027);Gain of helix (P = 0.027);.;.;.;Gain of helix (P = 0.027);.;Gain of helix (P = 0.027);.;.;Gain of helix (P = 0.027);Gain of helix (P = 0.027);
MVP		0.78
MPC		0.54
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.91
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-43314265;