NM_004213.5:c.437C>T

Variant names:

• chr15-84895099-C-T
• rs1020725971
• NM_004213.5:c.437C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004213.5(SLC28A1):​c.437C>T​(p.Pro146Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SLC28A1 NM_004213.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.276
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06952888).

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.437C>T	p.Pro146Leu	missense	Exon 6 of 19	NP_004204.3
	SLC28A1	NM_001287762.2		c.437C>T	p.Pro146Leu	missense	Exon 5 of 18	NP_001274691.1	O00337-1
	SLC28A1	NM_001321722.2		c.437C>T	p.Pro146Leu	missense	Exon 6 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.437C>T	p.Pro146Leu	missense	Exon 6 of 19	ENSP00000378074.1	O00337-1
	SLC28A1	ENST00000286749.3	TSL:1	c.437C>T	p.Pro146Leu	missense	Exon 5 of 18	ENSP00000286749.3	O00337-1
	SLC28A1	ENST00000338602.6	TSL:1	c.437C>T	p.Pro146Leu	missense	Exon 6 of 7	ENSP00000341629.2	O00337-2

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250868 AF XY: 0.00

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461540 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 727048

African (AFR) AF: 0.0000896 AC: 3 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111778

Other (OTH) AF: 0.0000331 AC: 2 AN: 60362

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152192 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74350

African (AFR) AF: 0.000241 AC: 10 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

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

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000567

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.1
DANN	Benign	0.43
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.28
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.13
Sift	Benign	0.32	T
Sift4G	Benign	0.21	T
Polyphen		0.80	P
Vest4		0.18
MutPred		0.34		Loss of glycosylation at P146 (P = 0.0314)
MVP		0.70
MPC		0.084
ClinPred		0.029	T
GERP RS		2.6
Varity_R		0.024
gMVP		0.15
Mutation Taster		=94/6	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: rs1020725971; hg19: chr15-85438330;