18-45731176-C-G

Variant summary

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

The NM_015865.7(SLC14A1):c.313C>G(p.Leu105Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,620 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: 0.0000014 (0 hom.)
• Consequence: SLC14A1 NM_015865.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.69

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 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/exons	MANE	UniProt
SLC14A1	NM_015865.7	c.313C>G	p.Leu105Val	missense_variant	4/10	ENST00000321925.9
LOC105372093	XR_935423.3	n.826+6290G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC14A1	ENST00000321925.9	c.313C>G	p.Leu105Val	missense_variant	4/10	1	NM_015865.7	P1
	ENST00000589510.5	n.160+6290G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461620 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727128

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Feb 15, 2023

The c.313C>G (p.L105V) alteration is located in exon 4 (coding exon 2) of the SLC14A1 gene. This alteration results from a C to G substitution at nucleotide position 313, causing the leucine (L) at amino acid position 105 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	Benign	0.087
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;.;T;.;.;T;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.58	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	2.9	M;.;.;M;.;.;M;.
MutationTaster	Benign	0.82	D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-2.3	N;.;N;.;.;N;.;.
REVEL	Benign	0.18
Sift	Benign	0.038	D;.;D;.;.;D;.;.
Sift4G	Benign	0.069	T;T;T;.;T;T;T;T
Polyphen		0.74	P;.;P;P;.;P;P;.
Vest4		0.38
MutPred		0.69		Gain of catalytic residue at L105 (P = 0.0378);Gain of catalytic residue at L105 (P = 0.0378);.;Gain of catalytic residue at L105 (P = 0.0378);Gain of catalytic residue at L105 (P = 0.0378);.;Gain of catalytic residue at L105 (P = 0.0378);Gain of catalytic residue at L105 (P = 0.0378);
MVP		0.49
MPC		0.34
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.51
gMVP		0.36

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: rs959314162; hg19: chr18-43311141;