18-45734360-T-G

Variant names:

• chr18-45734360-T-G
• rs1415543271
• NM_015865.7:c.428T>G

Variant summary

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

The NM_015865.7(SLC14A1):​c.428T>G​(p.Phe143Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC14A1 NM_015865.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08

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 Uncertain_significance. Variant got 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.428T>G	p.Phe143Cys	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.428T>G	p.Phe143Cys	missense_variant	Exon 5 of 10	1	NM_015865.7	ENSP00000318546.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251476 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135912

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461842 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727230

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: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.428T>G (p.F143C) alteration is located in exon 5 (coding exon 3) of the SLC14A1 gene. This alteration results from a T to G substitution at nucleotide position 428, causing the phenylalanine (F) at amino acid position 143 to be replaced by a cysteine (C). 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	0.33
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.26	T;T;T;.;.;T;.;.;.;.;T;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	.;T;D;.;.;.;D;D;T;D;T;.
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.64	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.4	M;.;.;.;.;M;.;.;.;.;M;.
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.4	D;.;D;D;.;.;D;D;D;.;.;.
REVEL	Benign	0.27
Sift	Uncertain	0.0020	D;.;D;D;.;.;D;D;D;.;.;.
Sift4G	Uncertain	0.0030	D;D;D;D;D;.;D;D;D;D;D;D
Polyphen		0.99	D;.;B;D;.;D;.;.;D;.;D;.
Vest4		0.46
MutPred		0.75		Gain of catalytic residue at W144 (P = 0.0208);Gain of catalytic residue at W144 (P = 0.0208);.;.;.;Gain of catalytic residue at W144 (P = 0.0208);.;.;.;.;Gain of catalytic residue at W144 (P = 0.0208);Gain of catalytic residue at W144 (P = 0.0208);
MVP		0.29
MPC		0.55
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.86
gMVP		0.89

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: rs1415543271; hg19: chr18-43314325; COSMIC: COSV58930875; COSMIC: COSV58930875;