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15-50574945-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_017672.6(TRPM7):c.4926G>A(p.Gly1642=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0473 in 1,613,802 control chromosomes in the GnomAD database, including 2,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.080 ( 808 hom., cov: 32)
Exomes 𝑓: 0.044 ( 2039 hom. )

Consequence

TRPM7
NM_017672.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0480
Variant links:
Genes affected
TRPM7 (HGNC:17994): (transient receptor potential cation channel subfamily M member 7) This gene belongs to the melastatin subfamily of transient receptor potential family of ion channels. The protein encoded by this gene is both an ion channel and a serine/threonine protein kinase. The kinase activity is essential for the ion channel function, which serves to increase intracellular calcium levels and to help regulate magnesium ion homeostasis. The encoded protein is involved in cytoskeletal organization, cell adhesion, cell migration and organogenesis. Defects in this gene are a cause of amyotrophic lateral sclerosis-parkinsonism/dementia complex of Guam. The gene may also be associated with defects of cardiac function. [provided by RefSeq, Aug 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-50574945-C-T is Benign according to our data. Variant chr15-50574945-C-T is described in ClinVar as [Benign]. Clinvar id is 3056472.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.048 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRPM7NM_017672.6 linkuse as main transcriptc.4926G>A p.Gly1642= synonymous_variant 34/39 ENST00000646667.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRPM7ENST00000646667.1 linkuse as main transcriptc.4926G>A p.Gly1642= synonymous_variant 34/39 NM_017672.6 A1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0801
AC:
12179
AN:
152032
Hom.:
808
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.184
Gnomad AMI
AF:
0.0110
Gnomad AMR
AF:
0.0617
Gnomad ASJ
AF:
0.0899
Gnomad EAS
AF:
0.00366
Gnomad SAS
AF:
0.0441
Gnomad FIN
AF:
0.0135
Gnomad MID
AF:
0.104
Gnomad NFE
AF:
0.0404
Gnomad OTH
AF:
0.0796
GnomAD3 exomes
AF:
0.0484
AC:
12062
AN:
249418
Hom.:
527
AF XY:
0.0478
AC XY:
6463
AN XY:
135320
show subpopulations
Gnomad AFR exome
AF:
0.189
Gnomad AMR exome
AF:
0.0386
Gnomad ASJ exome
AF:
0.0946
Gnomad EAS exome
AF:
0.00206
Gnomad SAS exome
AF:
0.0456
Gnomad FIN exome
AF:
0.0116
Gnomad NFE exome
AF:
0.0429
Gnomad OTH exome
AF:
0.0507
GnomAD4 exome
AF:
0.0439
AC:
64116
AN:
1461652
Hom.:
2039
Cov.:
33
AF XY:
0.0440
AC XY:
32024
AN XY:
727134
show subpopulations
Gnomad4 AFR exome
AF:
0.191
Gnomad4 AMR exome
AF:
0.0409
Gnomad4 ASJ exome
AF:
0.0960
Gnomad4 EAS exome
AF:
0.000630
Gnomad4 SAS exome
AF:
0.0476
Gnomad4 FIN exome
AF:
0.0119
Gnomad4 NFE exome
AF:
0.0404
Gnomad4 OTH exome
AF:
0.0533
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0801
AC:
12188
AN:
152150
Hom.:
808
Cov.:
32
AF XY:
0.0783
AC XY:
5822
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.184
Gnomad4 AMR
AF:
0.0616
Gnomad4 ASJ
AF:
0.0899
Gnomad4 EAS
AF:
0.00309
Gnomad4 SAS
AF:
0.0439
Gnomad4 FIN
AF:
0.0135
Gnomad4 NFE
AF:
0.0404
Gnomad4 OTH
AF:
0.0787
Alfa
AF:
0.0526
Hom.:
627
Bravo
AF:
0.0872
Asia WGS
AF:
0.0360
AC:
128
AN:
3478
EpiCase
AF:
0.0496
EpiControl
AF:
0.0526

ClinVar

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

Submissions by phenotype

TRPM7-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesDec 11, 2023This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
Cadd
Benign
4.5
Dann
Benign
0.65

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: rs16963774; hg19: chr15-50867142; API