Menu
GeneBe

rs16891982

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016180.5(SLC45A2):c.1122G>T(p.Leu374Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Benignin ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC45A2
NM_016180.5 missense

Scores

4
12
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55
Variant links:
Genes affected
SLC45A2 (HGNC:16472): (solute carrier family 45 member 2) This gene encodes a transporter protein that mediates melanin synthesis. The protein is expressed in a high percentage of melanoma cell lines. Mutations in this gene are a cause of oculocutaneous albinism type 4, and polymorphisms in this gene are associated with variations in skin and hair color. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC45A2NM_016180.5 linkuse as main transcriptc.1122G>T p.Leu374Phe missense_variant 5/7 ENST00000296589.9
SLC45A2NM_001012509.4 linkuse as main transcriptc.1122G>T p.Leu374Phe missense_variant 5/6
SLC45A2XM_047417259.1 linkuse as main transcriptc.882G>T p.Leu294Phe missense_variant 5/7
SLC45A2NM_001297417.4 linkuse as main transcriptc.*64G>T 3_prime_UTR_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC45A2ENST00000296589.9 linkuse as main transcriptc.1122G>T p.Leu374Phe missense_variant 5/71 NM_016180.5 P1Q9UMX9-1
SLC45A2ENST00000382102.7 linkuse as main transcriptc.1122G>T p.Leu374Phe missense_variant 5/61 Q9UMX9-4
SLC45A2ENST00000509381.1 linkuse as main transcriptc.*64G>T 3_prime_UTR_variant 4/41
SLC45A2ENST00000510600.1 linkuse as main transcriptc.597G>T p.Leu199Phe missense_variant 4/53

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152080
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461858
Hom.:
0
Cov.:
48
AF XY:
0.00
AC XY:
0
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152080
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.57
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
Cadd
Benign
23
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.74
D;.;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.71
T;T;T
M_CAP
Uncertain
0.15
D
MetaRNN
Uncertain
0.71
D;D;D
MetaSVM
Uncertain
0.61
D
MutationAssessor
Pathogenic
3.0
M;M;.
MutationTaster
Benign
1.0
D;D;D;D;N
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-2.7
D;D;D
REVEL
Pathogenic
0.70
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.0050
D;D;D
Polyphen
0.99
D;D;.
Vest4
0.20
MutPred
0.50
Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);.;
MVP
0.85
MPC
0.27
ClinPred
0.98
D
GERP RS
4.3
Varity_R
0.39
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs16891982; hg19: chr5-33951693; API