15-84887831-T-C

Variant names:

• chr15-84887831-T-C
• rs1427920379
• NM_004213.5:c.71T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004213.5(SLC28A1):​c.71T>C​(p.Met24Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,630 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M24L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034984887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A1	NM_004213.5	c.71T>C	p.Met24Thr	missense_variant	Exon 3 of 19	ENST00000394573.6	NP_004204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC28A1	ENST00000394573.6	c.71T>C	p.Met24Thr	missense_variant	Exon 3 of 19	1	NM_004213.5	ENSP00000378074.1
SLC28A1	ENST00000286749.3	c.71T>C	p.Met24Thr	missense_variant	Exon 2 of 18	1		ENSP00000286749.3
SLC28A1	ENST00000338602.6	c.71T>C	p.Met24Thr	missense_variant	Exon 3 of 7	1		ENSP00000341629.2
SLC28A1	ENST00000538177.5	c.71T>C	p.Met24Thr	missense_variant	Exon 2 of 15	2		ENSP00000443752.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461520 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727104

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111674

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74286

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.10
DANN	Benign	0.25
DEOGEN2	Benign	0.0074	.;T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.40	T;T;T;.
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.035	T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.0
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.54	N;N;N;N
REVEL	Benign	0.047
Sift	Benign	0.23	T;T;T;T
Sift4G	Benign	0.39	T;T;T;T
Polyphen		0.63	P;P;B;B
Vest4		0.17
MutPred		0.16		Loss of stability (P = 0.0104);Loss of stability (P = 0.0104);Loss of stability (P = 0.0104);Loss of stability (P = 0.0104);
MVP		0.17
MPC		0.088
ClinPred		0.22	T
GERP RS		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.067
gMVP		0.31
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1427920379; hg19: chr15-85431062;