Genetic Variant SLC49A4:p.Ala36Gly (chr3-122795299-C-G) – 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_032839.3(SLC49A4):c.107C>G(p.Ala36Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000155 in 1,291,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. A36V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

SLC49A4
NM_032839.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.345

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_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=0.043766588).

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.107C>G	p.Ala36Gly	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.107C>G	p.Ala36Gly	missense	Exon 1 of 9	ENSP00000261038.5	Q96SL1-1
SLC49A4	ENST00000477647.1	TSL:1	n.107C>G		non_coding_transcript_exon	Exon 1 of 8	ENSP00000418554.1	Q05BS2
SLC49A4	ENST00000864462.1		c.107C>G	p.Ala36Gly	missense	Exon 1 of 10	ENSP00000534521.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000155

AC:

AN:

1291726

Hom.:

Cov.:

AF XY:

0.00000315

AC XY:

AN XY:

635110

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24954

American (AMR)

AF:

0.00

AC:

AN:

15496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20368

East Asian (EAS)

AF:

0.00

AC:

AN:

29322

South Asian (SAS)

AF:

0.0000302

AC:

AN:

66214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3706

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1043208

Other (OTH)

AF:

0.00

AC:

AN:

53502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.0049

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.42

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.38

M_CAP

Benign

0.066

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.62

PhyloP100

0.34

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.29

REVEL

Benign

0.13

Sift

Benign

0.27

Sift4G

Benign

0.39

Vest4

0.073

MutPred

0.32

Gain of loop (P = 0.0045)

MVP

0.17

MPC

1.5

ClinPred

0.11

GERP RS

1.0

PromoterAI

-0.071

Neutral

(source)

gMVP

0.34

Mutation Taster

=94/6

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over