18-45739554-G-C

Variant names:

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

Variant summary

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

The NM_015865.7(SLC14A1):​c.838G>C​(p.Asp280His) 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. 15/24 in silico tools predict 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015865.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC14A1	NM_015865.7	MANE Select	c.838G>C	p.Asp280His	missense	Exon 8 of 10	NP_056949.4
	SLC14A1	NM_001128588.4		c.1006G>C	p.Asp336His	missense	Exon 9 of 11	NP_001122060.3
	SLC14A1	NM_001146037.1		c.1006G>C	p.Asp336His	missense	Exon 7 of 9	NP_001139509.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC14A1	ENST00000321925.9	TSL:1 MANE Select	c.838G>C	p.Asp280His	missense	Exon 8 of 10	ENSP00000318546.4
	SLC14A1	ENST00000586142.5	TSL:1	c.838G>C	p.Asp280His	missense	Exon 6 of 8	ENSP00000470476.1
	SLC14A1	ENST00000589700.5	TSL:1	c.690G>C	p.Arg230Ser	missense	Exon 5 of 7	ENSP00000465044.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.72
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.17
Sift	Benign	0.11	T
Sift4G	Benign	0.092	T
Polyphen		0.86	P
Vest4		0.23
MutPred		0.25		Gain of sheet (P = 0.0477)
MVP		0.51
MPC		0.32
ClinPred		0.64	D
GERP RS		-7.6
Varity_R		0.32
gMVP		0.74
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.21		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;