chr15-84904200-G-C

Position:

• chr15-84904200-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004213.5(SLC28A1):​c.565G>C​(p.Val189Leu) 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. 15/21 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. V189I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC28A1 NM_004213.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.852

Genes affected

SLC28A1 (HGNC:11001): (solute carrier family 28 member 1) Enables azole transmembrane transporter activity; cytidine transmembrane transporter activity; and uridine transmembrane transporter activity. Involved in azole transmembrane transport; nucleoside transport; and pyrimidine-containing compound transmembrane transport. Located in cytosol; nuclear speck; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044900715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC28A1	NM_004213.5	c.565G>C	p.Val189Leu	missense_variant	7/19	ENST00000394573.6	NP_004204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC28A1	ENST00000394573.6	c.565G>C	p.Val189Leu	missense_variant	7/19	1	NM_004213.5	ENSP00000378074.1
SLC28A1	ENST00000286749.3	c.565G>C	p.Val189Leu	missense_variant	6/18	1		ENSP00000286749.3
SLC28A1	ENST00000538177.5	c.565G>C	p.Val189Leu	missense_variant	6/15	2		ENSP00000443752.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.0090
DANN	Benign	0.50
DEOGEN2	Benign	0.018	T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.17	T;T;.
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.045	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.28	.;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.026
Sift	Benign	0.49	T;T;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.011	B;B;B
Vest4		0.098
MutPred		0.38		Loss of catalytic residue at V189 (P = 0.1104);Loss of catalytic residue at V189 (P = 0.1104);Loss of catalytic residue at V189 (P = 0.1104);
MVP		0.16
MPC		0.076
ClinPred		0.086	T
GERP RS		-5.9
Varity_R		0.088
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2290272; hg19: chr15-85447431;