NM_016180.5:c.1122G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016180.5(SLC45A2):c.1122G>C(p.Leu374Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 1,613,970 control chromosomes in the GnomAD database, including 626,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 42245 hom., cov: 32)

Exomes 𝑓: 0.84 ( 584751 hom. )

Consequence

SLC45A2
NM_016180.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.55

Publications

324 publications found

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]

SLC45A2 Gene-Disease associations (from GenCC):

oculocutaneous albinism type 4
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia

SLC45A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6710072E-6).

BP6

Variant 5-33951588-C-G is Benign according to our data. Variant chr5-33951588-C-G is described in ClinVar as Benign. ClinVar VariationId is 197829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016180.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC45A2	NM_016180.5	MANE Select	c.1122G>C	p.Leu374Phe	missense	Exon 5 of 7	NP_057264.4
SLC45A2	NM_001012509.4		c.1122G>C	p.Leu374Phe	missense	Exon 5 of 6	NP_001012527.2	Q9UMX9-4
SLC45A2	NM_001297417.4		c.*64G>C		3_prime_UTR	Exon 4 of 4	NP_001284346.2	D6RGY6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC45A2	ENST00000296589.9	TSL:1 MANE Select	c.1122G>C	p.Leu374Phe	missense	Exon 5 of 7	ENSP00000296589.4	Q9UMX9-1
SLC45A2	ENST00000382102.7	TSL:1	c.1122G>C	p.Leu374Phe	missense	Exon 5 of 6	ENSP00000371534.3	Q9UMX9-4
SLC45A2	ENST00000509381.1	TSL:1	c.*64G>C		3_prime_UTR	Exon 4 of 4	ENSP00000421100.1	D6RGY6

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

97057

AN:

152040

Hom.:

42249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.990

Gnomad AMR

AF:

0.551

Gnomad ASJ

AF:

0.913

Gnomad EAS

AF:

0.00578

Gnomad SAS

AF:

0.0968

Gnomad FIN

AF:

0.984

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.962

Gnomad OTH

AF:

0.616

GnomAD2 exomes

AF:

0.645

AC:

162176

AN:

251420

AF XY:

0.645

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.381

Gnomad ASJ exome

AF:

0.910

Gnomad EAS exome

AF:

0.00169

Gnomad FIN exome

AF:

0.982

Gnomad NFE exome

AF:

0.955

Gnomad OTH exome

AF:

0.737

GnomAD4 exome

AF:

0.844

AC:

1233469

AN:

1461812

Hom.:

584751

Cov.:

AF XY:

0.825

AC XY:

599788

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.130

AC:

4335

AN:

33474

American (AMR)

AF:

0.402

AC:

17972

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.911

AC:

23802

AN:

26136

East Asian (EAS)

AF:

0.00134

AC:

AN:

39698

South Asian (SAS)

AF:

0.103

AC:

8925

AN:

86254

European-Finnish (FIN)

AF:

0.981

AC:

52424

AN:

53420

Middle Eastern (MID)

AF:

0.391

AC:

2253

AN:

5766

European-Non Finnish (NFE)

AF:

0.969

AC:

1078045

AN:

1111962

Other (OTH)

AF:

0.756

AC:

45660

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

3907

7814

11721

15628

19535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20694

41388

62082

82776

103470

<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

AF:

0.638

AC:

97039

AN:

152158

Hom.:

42245

Cov.:

AF XY:

0.623

AC XY:

46392

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.163

AC:

6755

AN:

41460

American (AMR)

AF:

0.550

AC:

8406

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.913

AC:

3165

AN:

3468

East Asian (EAS)

AF:

0.00560

AC:

AN:

5174

South Asian (SAS)

AF:

0.0990

AC:

477

AN:

4818

European-Finnish (FIN)

AF:

0.984

AC:

10452

AN:

10622

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.962

AC:

65426

AN:

68014

Other (OTH)

AF:

0.609

AC:

1288

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

624

1247

1871

2494

3118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.866

Hom.:

16369

Bravo

AF:

0.589

TwinsUK

AF:

0.971

AC:

3601

ALSPAC

AF:

0.965

AC:

3720

ESP6500AA

AF:

0.185

AC:

814

ESP6500EA

AF:

0.959

AC:

8249

ExAC

AF:

0.640

AC:

77701

Asia WGS

AF:

0.0910

AC:

322

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Oculocutaneous albinism type 4 (1)

Oculocutaneous albinism type 4;C2673584:SKIN/HAIR/EYE PIGMENTATION 5, BLACK/NONBLACK HAIR (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Uncertain

0.040

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0000017

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.0

PhyloP100

1.5

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.7

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Polyphen

0.99

Vest4

0.20

MutPred

0.50

Gain of helix (P = 0.2294)

MPC

0.27

ClinPred

0.029

GERP RS

4.3

Varity_R

0.39

gMVP

0.90

Mutation Taster

=44/56

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over