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15-50574885-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_017672.6(TRPM7):c.4986C>T(p.Tyr1662=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,610,592 control chromosomes in the GnomAD database, including 256,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.59 ( 26797 hom., cov: 33)
Exomes 𝑓: 0.56 ( 229330 hom. )

Consequence

TRPM7
NM_017672.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.07
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 -15 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=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-50574885-G-A is Benign according to our data. Variant chr15-50574885-G-A is described in ClinVar as [Benign]. Clinvar id is 1256704.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=2.07 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 = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRPM7NM_017672.6 linkuse as main transcriptc.4986C>T p.Tyr1662= synonymous_variant 34/39 ENST00000646667.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRPM7ENST00000646667.1 linkuse as main transcriptc.4986C>T p.Tyr1662= synonymous_variant 34/39 NM_017672.6 A1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.590
AC:
89712
AN:
151942
Hom.:
26777
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.665
Gnomad AMI
AF:
0.609
Gnomad AMR
AF:
0.632
Gnomad ASJ
AF:
0.555
Gnomad EAS
AF:
0.571
Gnomad SAS
AF:
0.560
Gnomad FIN
AF:
0.475
Gnomad MID
AF:
0.608
Gnomad NFE
AF:
0.558
Gnomad OTH
AF:
0.614
GnomAD3 exomes
AF:
0.570
AC:
141859
AN:
248956
Hom.:
40905
AF XY:
0.569
AC XY:
76918
AN XY:
135080
show subpopulations
Gnomad AFR exome
AF:
0.672
Gnomad AMR exome
AF:
0.624
Gnomad ASJ exome
AF:
0.549
Gnomad EAS exome
AF:
0.555
Gnomad SAS exome
AF:
0.571
Gnomad FIN exome
AF:
0.471
Gnomad NFE exome
AF:
0.563
Gnomad OTH exome
AF:
0.566
GnomAD4 exome
AF:
0.559
AC:
815161
AN:
1458530
Hom.:
229330
Cov.:
37
AF XY:
0.560
AC XY:
406343
AN XY:
725754
show subpopulations
Gnomad4 AFR exome
AF:
0.670
Gnomad4 AMR exome
AF:
0.621
Gnomad4 ASJ exome
AF:
0.551
Gnomad4 EAS exome
AF:
0.558
Gnomad4 SAS exome
AF:
0.573
Gnomad4 FIN exome
AF:
0.480
Gnomad4 NFE exome
AF:
0.555
Gnomad4 OTH exome
AF:
0.565
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.590
AC:
89785
AN:
152062
Hom.:
26797
Cov.:
33
AF XY:
0.589
AC XY:
43804
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.665
Gnomad4 AMR
AF:
0.632
Gnomad4 ASJ
AF:
0.555
Gnomad4 EAS
AF:
0.570
Gnomad4 SAS
AF:
0.560
Gnomad4 FIN
AF:
0.475
Gnomad4 NFE
AF:
0.558
Gnomad4 OTH
AF:
0.611
Alfa
AF:
0.565
Hom.:
20363
Bravo
AF:
0.605
Asia WGS
AF:
0.561
AC:
1950
AN:
3478
EpiCase
AF:
0.580
EpiControl
AF:
0.583

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 testingGeneDxNov 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
3.2
Dann
Benign
0.52
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs473357; hg19: chr15-50867082; API