15-31001273-A-G

Position:

chr15-31001273-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001252024.2(TRPM1):c.*549T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00514 in 147,670 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRPM1
NM_001252024.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.28

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 15-31001273-A-G is Benign according to our data. Variant chr15-31001273-A-G is described in ClinVar as [Benign]. Clinvar id is 888458.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00514 (759/147670) while in subpopulation AFR AF= 0.0181 (724/39994). AF 95% confidence interval is 0.017. There are 4 homozygotes in gnomad4. There are 360 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
TRPM1	NM_001252024.2 linkuse as main transcript	c.*549T>C	3_prime_UTR_variant	28/28	ENST00000256552.11	NP_001238953.1
TRPM1	NM_001252020.2 linkuse as main transcript	c.*549T>C	3_prime_UTR_variant	27/27		NP_001238949.1
TRPM1	NM_002420.6 linkuse as main transcript	c.*549T>C	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.*549T>C		3_prime_UTR_variant	28/28	1	NM_001252024.2	ENSP00000256552	P4	Q7Z4N2-6
	ENST00000665655.1 linkuse as main transcript	n.71+9032A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00514

AC:

758

AN:

147580

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00135

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000432

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000750

Gnomad OTH

AF:

0.00393

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AMR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

GnomAD4 genome

AF:

0.00514

AC:

759

AN:

147670

Hom.:

Cov.:

AF XY:

0.00501

AC XY:

360

AN XY:

71884

show subpopulations

Gnomad4 AFR

AF:

0.0181

Gnomad4 AMR

AF:

0.00134

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000432

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000750

Gnomad4 OTH

AF:

0.00389

Alfa

AF:

0.00320

Hom.:

Bravo

AF:

0.00534

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital stationary night blindness 1C

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.46

DANN

Benign

0.56

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