dbSNP rs11854484: SLC28A2:p.Pro22Gln (chr15-45253280-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004212.4(SLC28A2):c.65C>A(p.Pro22Gln) 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. 16/22 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. P22L) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC28A2
NM_004212.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.79

Publications

52 publications found

Variant links:

Genes affected

SLC28A2 (HGNC:11002): (solute carrier family 28 member 2) Enables neurotransmitter transmembrane transporter activity and nucleoside transmembrane transporter activity. Involved in several processes, including nucleoside transport; purine nucleobase transmembrane transport; and pyrimidine-containing compound transmembrane transport. Predicted to be located in membrane. Predicted to be part of brush border membrane; coated vesicle; and vesicle membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC28A2 links:

SLC28A2-AS1 (HGNC:55417): (SLC28A2 antisense RNA 1)

SLC28A2-AS1 links:

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ACMG classification

Classification was made for transcript

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=0.039950848).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004212.4. 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
	SLC28A2	NM_004212.4	MANE Select	c.65C>A	p.Pro22Gln	missense	Exon 2 of 18	NP_004203.2
	SLC28A2-AS1	NR_120335.1		n.180+586G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC28A2	ENST00000347644.8	TSL:1 MANE Select	c.65C>A	p.Pro22Gln	missense	Exon 2 of 18	ENSP00000315006.4
SLC28A2	ENST00000959719.1		c.65C>A	p.Pro22Gln	missense	Exon 2 of 18	ENSP00000629778.1
SLC28A2	ENST00000959720.1		c.65C>A	p.Pro22Gln	missense	Exon 2 of 17	ENSP00000629779.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1460138

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726404

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110562

Other (OTH)

AF:

0.00

AC:

AN:

60352

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

92380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.0

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.011

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.41

M_CAP

Benign

0.0034

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

PhyloP100

-1.8

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.44

REVEL

Benign

0.059

Sift

Benign

0.66

Sift4G

Benign

0.59

Polyphen

0.50

Vest4

0.15

MutPred

0.16

Gain of helix (P = 0.027)

MVP

0.12

MPC

0.040

ClinPred

0.11

GERP RS

-0.81

Varity_R

0.028

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over