Genetic Variant SLC45A4:p.Asn613Ile (chr8-141215862-T-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001286646.2(SLC45A4):c.1838A>T(p.Asn613Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. N613S) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC45A4
NM_001286646.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.04

Publications

0 publications found

Variant links:

Genes affected

SLC45A4 (HGNC:29196): (solute carrier family 45 member 4) Predicted to enable sucrose:proton symporter activity. Predicted to be involved in sucrose transport. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC45A4 links:

ENSG00000296050 (HGNC:):

ENSG00000296050 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.869

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC45A4	NM_001286646.2 link	c.1838A>T	p.Asn613Ile	missense_variant	Exon 7 of 9	ENST00000517878.6	NP_001273575.1	Q5BKX6E7EV90B2RXG1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC45A4	ENST00000517878.6 link	c.1838A>T	p.Asn613Ile	missense_variant	Exon 7 of 9	1	NM_001286646.2	ENSP00000428137.1	E7EV90
SLC45A4	ENST00000024061.7 link	c.1685A>T	p.Asn562Ile	missense_variant	Exon 6 of 8	1		ENSP00000024061.3	Q5BKX6-3
SLC45A4	ENST00000519067.5 link	c.1685A>T	p.Asn562Ile	missense_variant	Exon 6 of 7	1		ENSP00000429059.1	Q5BKX6-2
ENSG00000296050	ENST00000735948.1 link	n.133-6737T>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112008

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.13

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;T;.

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Pathogenic

0.30

MetaRNN

Pathogenic

0.87

D;D;D

MetaSVM

Pathogenic

0.96

PhyloP100

6.0

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-8.0

D;D;D

REVEL

Pathogenic

0.70

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.95

P;P;D

Vest4

0.79

MutPred

0.56

.;Gain of sheet (P = 0.0827);.;

MVP

0.90

MPC

0.89

ClinPred

1.0

GERP RS

4.2

gMVP

0.91

Mutation Taster

=46/54

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over