chr15-84888842-C-G

Variant names:

• chr15-84888842-C-G
• rs1196209657
• NM_004213.5:c.167C>G

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.167C>G​(p.Pro56Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,400,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P56L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC28A1 NM_004213.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0900
• 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=0.06376156).

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.167C>G	p.Pro56Arg	missense	Exon 4 of 19	NP_004204.3
	SLC28A1	NM_001287762.2		c.167C>G	p.Pro56Arg	missense	Exon 3 of 18	NP_001274691.1	O00337-1
	SLC28A1	NM_001321722.2		c.167C>G	p.Pro56Arg	missense	Exon 4 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.167C>G	p.Pro56Arg	missense	Exon 4 of 19	ENSP00000378074.1	O00337-1
	SLC28A1	ENST00000286749.3	TSL:1	c.167C>G	p.Pro56Arg	missense	Exon 3 of 18	ENSP00000286749.3	O00337-1
	SLC28A1	ENST00000338602.6	TSL:1	c.167C>G	p.Pro56Arg	missense	Exon 4 of 7	ENSP00000341629.2	O00337-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1400256 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690840

African (AFR) AF: 0.00 AC: 0 AN: 31662

American (AMR) AF: 0.00 AC: 0 AN: 35868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25184

East Asian (EAS) AF: 0.00 AC: 0 AN: 35834

South Asian (SAS) AF: 0.00 AC: 0 AN: 79256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079434

Other (OTH) AF: 0.0000172 AC: 1 AN: 58038

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

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	0.070
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.4
DANN	Benign	0.29
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.090
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.14
Sift	Benign	0.52	T
Sift4G	Benign	0.68	T
Polyphen		0.14	B
Vest4		0.091
MutPred		0.24		Gain of MoRF binding (P = 0.0056)
MVP		0.22
MPC		0.082
ClinPred		0.069	T
GERP RS		0.13
Varity_R		0.025
gMVP		0.14
Mutation Taster		=96/4	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: rs1196209657; hg19: chr15-85432073;