18-45731082-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015865.7(SLC14A1):c.219C>A(p.Asn73Lys) 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 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: 2.17

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC14A1	NM_015865.7	c.219C>A	p.Asn73Lys	missense_variant	4/10	ENST00000321925.9
LOC105372093	XR_935423.3	n.826+6384G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC14A1	ENST00000321925.9	c.219C>A	p.Asn73Lys	missense_variant	4/10	1	NM_015865.7	P1
	ENST00000589510.5	n.160+6384G>T		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

Aug 01, 2022

The c.219C>A (p.N73K) alteration is located in exon 4 (coding exon 2) of the SLC14A1 gene. This alteration results from a C to A substitution at nucleotide position 219, causing the asparagine (N) at amino acid position 73 to be replaced by a lysine (K). 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	0.50
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T;.;T;.;.;T;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.77	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.9	M;.;.;M;.;.;M;.
MutationTaster	Benign	1.0	D;D;D;D;N;N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-4.6	D;.;D;.;.;D;.;.
REVEL	Uncertain	0.30
Sift	Uncertain	0.0020	D;.;D;.;.;D;.;.
Sift4G	Uncertain	0.0030	D;T;D;D;D;D;D;T
Polyphen		0.97	D;.;P;D;.;P;D;.
Vest4		0.63
MutPred		0.81		Gain of methylation at N73 (P = 0.0087);Gain of methylation at N73 (P = 0.0087);.;Gain of methylation at N73 (P = 0.0087);Gain of methylation at N73 (P = 0.0087);.;Gain of methylation at N73 (P = 0.0087);Gain of methylation at N73 (P = 0.0087);
MVP		0.54
MPC		0.54
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.88
gMVP		0.45

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: chr18-43311047;