chr21-44364258-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003307.4(TRPM2):​c.399G>A​(p.Thr133=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,614,166 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 51 hom., cov: 33)
Exomes 𝑓: 0.0016 ( 45 hom. )

Consequence

TRPM2
NM_003307.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.63
Variant links:
Genes affected
TRPM2 (HGNC:12339): (transient receptor potential cation channel subfamily M member 2) The protein encoded by this gene forms a tetrameric cation channel that is permeable to calcium, sodium, and potassium and is regulated by free intracellular ADP-ribose. The encoded protein is activated by oxidative stress and confers susceptibility to cell death. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. Additional transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 21-44364258-G-A is Benign according to our data. Variant chr21-44364258-G-A is described in ClinVar as [Benign]. Clinvar id is 785674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.63 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRPM2NM_003307.4 linkuse as main transcriptc.399G>A p.Thr133= synonymous_variant 3/32 ENST00000397928.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRPM2ENST00000397928.6 linkuse as main transcriptc.399G>A p.Thr133= synonymous_variant 3/321 NM_003307.4 P1O94759-1

Frequencies

GnomAD3 genomes
AF:
0.0156
AC:
2380
AN:
152202
Hom.:
53
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0542
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00647
Gnomad ASJ
AF:
0.00346
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00621
GnomAD3 exomes
AF:
0.00430
AC:
1080
AN:
251436
Hom.:
24
AF XY:
0.00299
AC XY:
406
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.0548
Gnomad AMR exome
AF:
0.00347
Gnomad ASJ exome
AF:
0.00268
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000193
Gnomad OTH exome
AF:
0.00310
GnomAD4 exome
AF:
0.00160
AC:
2338
AN:
1461846
Hom.:
45
Cov.:
31
AF XY:
0.00139
AC XY:
1009
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.0514
Gnomad4 AMR exome
AF:
0.00373
Gnomad4 ASJ exome
AF:
0.00279
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000112
Gnomad4 OTH exome
AF:
0.00364
GnomAD4 genome
AF:
0.0156
AC:
2380
AN:
152320
Hom.:
51
Cov.:
33
AF XY:
0.0146
AC XY:
1090
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0540
Gnomad4 AMR
AF:
0.00640
Gnomad4 ASJ
AF:
0.00346
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00615
Alfa
AF:
0.00736
Hom.:
20
Bravo
AF:
0.0177
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.20
DANN
Benign
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs45551339; hg19: chr21-45784141; API