Variant 15-31001792-T-TA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The ENST00000256552.11(TRPM1):c.*29_*30insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00977 in 1,129,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.011 ( 0 hom. )

Consequence

TRPM1
ENST00000256552.11 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.44

Variant links:

Genes affected

TRPM1 (HGNC:7146): (transient receptor potential cation channel subfamily M member 1) This gene encodes a member of the transient receptor potential melastatin subfamily of transient receptor potential ion channels. The encoded protein is a calcium permeable cation channel that is expressed in melanocytes and may play a role in melanin synthesis. Specific mutations in this gene are the cause autosomal recessive complete congenital stationary night blindness-1C. The expression of this protein is inversely correlated with melanoma aggressiveness and as such it is used as a prognostic marker for melanoma metastasis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]

TRPM1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0112 (10985/980424) while in subpopulation NFE AF= 0.0119 (8878/745492). AF 95% confidence interval is 0.0117. There are 0 homozygotes in gnomad4_exome. There are 5195 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
TRPM1	NM_001252024.2 linkuse as main transcript	c.29_30insT	3_prime_UTR_variant	28/28	ENST00000256552.11	NP_001238953.1
TRPM1	NM_001252020.2 linkuse as main transcript	c.29_30insT	3_prime_UTR_variant	27/27		NP_001238949.1
TRPM1	NM_002420.6 linkuse as main transcript	c.29_30insT	3_prime_UTR_variant	27/27		NP_002411.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM1	ENST00000256552.11 linkuse as main transcript	c.29_30insT		3_prime_UTR_variant	28/28	1	NM_001252024.2	ENSP00000256552	P4	Q7Z4N2-6
	ENST00000665655.1 linkuse as main transcript	n.71+9562dup		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

149130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00141

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000583

Gnomad SAS

AF:

0.000211

Gnomad FIN

AF:

0.000204

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000194

Gnomad OTH

AF:

0.000492

GnomAD4 exome

AF:

0.0112

AC:

10985

AN:

980424

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

5195

AN XY:

487944

show subpopulations

Gnomad4 AFR exome

AF:

0.00894

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.00986

Gnomad4 EAS exome

AF:

0.00374

Gnomad4 SAS exome

AF:

0.00991

Gnomad4 FIN exome

AF:

0.00759

Gnomad4 NFE exome

AF:

0.0119

Gnomad4 OTH exome

AF:

0.00963

GnomAD4 genome

AF:

0.000335

AC:

AN:

149206

Hom.:

Cov.:

AF XY:

0.000412

AC XY:

AN XY:

72732

show subpopulations

Gnomad4 AFR

AF:

0.000220

Gnomad4 AMR

AF:

0.00140

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000585

Gnomad4 SAS

AF:

0.000211

Gnomad4 FIN

AF:

0.000204

Gnomad4 NFE

AF:

0.000194

Gnomad4 OTH

AF:

0.000487

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital Stationary Night Blindness, Recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over