Genetic Variant SLC67A1:p.Arg12Pro (chr11-2903380-G-C) – 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_002555.6(SLC67A1):c.35G>C(p.Arg12Pro) 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.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

SLC67A1
NM_002555.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00800

Publications

48 publications found

Variant links:

Genes affected

SLC67A1 (HGNC:10964): (solute carrier family 22 member 18) This gene is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene is imprinted, with preferential expression from the maternal allele. Mutations in this gene have been found in Wilms' tumor and lung cancer. This protein may act as a transporter of organic cations, and have a role in the transport of chloroquine and quinidine-related compounds in kidney. Several alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Oct 2015]

SLC67A1 links:

SLC22A18AS (HGNC:10965): (SLC22A18 antisense RNA)

SLC22A18AS links:

Genome browser will be placed here

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=0.057914943).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002555.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC67A1	NM_002555.6	MANE Select	c.35G>C	p.Arg12Pro	missense	Exon 2 of 11	NP_002546.3
SLC67A1	NM_001315501.2		c.290G>C	p.Arg97Pro	missense	Exon 2 of 11	NP_001302430.1
SLC67A1	NM_183233.3		c.35G>C	p.Arg12Pro	missense	Exon 2 of 11	NP_899056.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC22A18	ENST00000649076.2	MANE Select	c.35G>C	p.Arg12Pro	missense	Exon 2 of 11	ENSP00000497561.1
SLC22A18	ENST00000347936.6	TSL:1	c.35G>C	p.Arg12Pro	missense	Exon 2 of 11	ENSP00000307859.2
SLC22A18	ENST00000380574.5	TSL:1	c.35G>C	p.Arg12Pro	missense	Exon 2 of 11	ENSP00000369948.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151910

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151910

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74202

African (AFR)

AF:

0.00

AC:

AN:

41326

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67938

Other (OTH)

AF:

0.00

AC:

AN:

2094

Alfa

AF:

0.00

Hom.:

47487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.2

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.39

M_CAP

Benign

0.026

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

0.0080

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.70

REVEL

Benign

0.018

Sift

Uncertain

0.024

Sift4G

Uncertain

0.018

Polyphen

0.0

Vest4

0.096

MutPred

0.32

Loss of MoRF binding (P = 2e-04)

MVP

0.17

MPC

0.25

ClinPred

0.10

GERP RS

-1.5

PromoterAI

0.030

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.37

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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