rs2069391

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_006928.5(PMEL):​c.-51-32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 1,604,622 control chromosomes in the GnomAD database, including 4,920 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.075 ( 487 hom., cov: 32)
Exomes 𝑓: 0.076 ( 4433 hom. )

Consequence

PMEL
NM_006928.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.103
Variant links:
Genes affected
PMEL (HGNC:10880): (premelanosome protein) This gene encodes a melanocyte-specific type I transmembrane glycoprotein. The encoded protein is enriched in melanosomes, which are the melanin-producing organelles in melanocytes, and plays an essential role in the structural organization of premelanosomes. This protein is involved in generating internal matrix fibers that define the transition from Stage I to Stage II melanosomes. This protein undergoes a complex pattern of prosttranslational processing and modification that is essential to the proper functioning of the protein. A secreted form of this protein that is released by proteolytic ectodomain shedding may be used as a melanoma-specific serum marker. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PMELNM_006928.5 linkuse as main transcriptc.-51-32G>A intron_variant NP_008859.1 P40967-1
PMELNM_001200054.1 linkuse as main transcriptc.-83G>A upstream_gene_variant NP_001186983.1 P40967-2
PMELNM_001320121.1 linkuse as main transcriptc.-83G>A upstream_gene_variant NP_001307050.1 P40967-5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PMELENST00000548493.5 linkuse as main transcriptc.-51-32G>A intron_variant 2 ENSP00000447374.1 P40967-1
PMELENST00000552882.5 linkuse as main transcriptc.-51-32G>A intron_variant 5 ENSP00000449690.1 P40967-1
PMELENST00000549418.5 linkuse as main transcriptc.-51-32G>A intron_variant 4 ENSP00000446633.1 F8VZV2

Frequencies

GnomAD3 genomes
AF:
0.0746
AC:
11347
AN:
152162
Hom.:
486
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0885
Gnomad AMI
AF:
0.0965
Gnomad AMR
AF:
0.0535
Gnomad ASJ
AF:
0.0769
Gnomad EAS
AF:
0.00520
Gnomad SAS
AF:
0.0575
Gnomad FIN
AF:
0.0689
Gnomad MID
AF:
0.0981
Gnomad NFE
AF:
0.0779
Gnomad OTH
AF:
0.0683
GnomAD4 exome
AF:
0.0760
AC:
110376
AN:
1452342
Hom.:
4433
Cov.:
30
AF XY:
0.0750
AC XY:
54209
AN XY:
722314
show subpopulations
Gnomad4 AFR exome
AF:
0.0917
Gnomad4 AMR exome
AF:
0.0541
Gnomad4 ASJ exome
AF:
0.0750
Gnomad4 EAS exome
AF:
0.00437
Gnomad4 SAS exome
AF:
0.0566
Gnomad4 FIN exome
AF:
0.0738
Gnomad4 NFE exome
AF:
0.0807
Gnomad4 OTH exome
AF:
0.0740
GnomAD4 genome
AF:
0.0745
AC:
11348
AN:
152280
Hom.:
487
Cov.:
32
AF XY:
0.0737
AC XY:
5491
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.0883
Gnomad4 AMR
AF:
0.0534
Gnomad4 ASJ
AF:
0.0769
Gnomad4 EAS
AF:
0.00522
Gnomad4 SAS
AF:
0.0575
Gnomad4 FIN
AF:
0.0689
Gnomad4 NFE
AF:
0.0779
Gnomad4 OTH
AF:
0.0666
Alfa
AF:
0.0748
Hom.:
486
Bravo
AF:
0.0740
Asia WGS
AF:
0.0290
AC:
100
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
CADD
Benign
14
DANN
Benign
0.89

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

LitVar

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

Other links and lift over

dbSNP: rs2069391; hg19: chr12-56359878; API