dbSNP rs1030343099: SLC49A4:p.Arg51Cys (chr3-122795343-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_032839.3(SLC49A4):c.151C>T(p.Arg51Cys) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC49A4
NM_032839.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82

Publications

0 publications found

Variant links:

Genes affected

SLC49A4 (HGNC:16628): (solute carrier family 49 member 4) This gene encodes a membrane-bound protein from the major facilitator superfamily of transporters. Disruption of this gene by translocation has been associated with haplo-insufficiency and renal cell carcinomas. Alternatively spliced transcript variants have been described, but their biological validity has not yet been determined. [provided by RefSeq, Jul 2008]

SLC49A4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.943

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032839.3. 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
	SLC49A4	NM_032839.3	MANE Select	c.151C>T	p.Arg51Cys	missense	Exon 1 of 9	NP_116228.1	Q96SL1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC49A4	ENST00000261038.6	TSL:1 MANE Select	c.151C>T	p.Arg51Cys	missense	Exon 1 of 9	ENSP00000261038.5	Q96SL1-1
SLC49A4	ENST00000477647.1	TSL:1	n.151C>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000418554.1	Q05BS2
SLC49A4	ENST00000864462.1		c.151C>T	p.Arg51Cys	missense	Exon 1 of 10	ENSP00000534521.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1409084

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700476

African (AFR)

AF:

0.00

AC:

AN:

29554

American (AMR)

AF:

0.00

AC:

AN:

37952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24814

East Asian (EAS)

AF:

0.00

AC:

AN:

35032

South Asian (SAS)

AF:

0.00

AC:

AN:

81420

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43844

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4116

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094098

Other (OTH)

AF:

0.00

AC:

AN:

58254

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.63

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.96

MetaRNN

Pathogenic

0.94

MetaSVM

Benign

-0.43

PhyloP100

1.8

PrimateAI

Pathogenic

0.93

PROVEAN

Pathogenic

-6.2

REVEL

Uncertain

0.58

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Vest4

0.82

MutPred

0.77

Loss of MoRF binding (P = 0.0084)

MVP

0.30

MPC

3.3

ClinPred

1.0

GERP RS

2.4

PromoterAI

-0.076

Neutral

(source)

gMVP

0.95

Mutation Taster

=76/24

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