15-84935498-G-C

Variant names:

• chr15-84935498-G-C
• rs2242046
• NM_004213.5:c.1561G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004213.5(SLC28A1):​c.1561G>C​(p.Asp521His) 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. 15/22 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. D521N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC28A1 NM_004213.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14243549).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004213.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A1	NM_004213.5	MANE Select	c.1561G>C	p.Asp521His	missense	Exon 15 of 19	NP_004204.3
	SLC28A1	NM_001287762.2		c.1561G>C	p.Asp521His	missense	Exon 14 of 18	NP_001274691.1	O00337-1
	SLC28A1	NM_001321722.2		c.1561G>C	p.Asp521His	missense	Exon 15 of 19	NP_001308651.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A1	ENST00000394573.6	TSL:1 MANE Select	c.1561G>C	p.Asp521His	missense	Exon 15 of 19	ENSP00000378074.1	O00337-1
	SLC28A1	ENST00000286749.3	TSL:1	c.1561G>C	p.Asp521His	missense	Exon 14 of 18	ENSP00000286749.3	O00337-1
	SLC28A1	ENST00000859184.1		c.1561G>C	p.Asp521His	missense	Exon 15 of 19	ENSP00000529243.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.85	L
PhyloP100		1.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.050
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.015	D
Polyphen		0.86	P
Vest4		0.14
MutPred		0.31		Gain of MoRF binding (P = 0.0454)
MVP		0.31
MPC		0.29
ClinPred		0.37	T
GERP RS		-0.14
Varity_R		0.093
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2242046; hg19: chr15-85478729;