Genetic Variant TRPM7:c.2989-1621C>A (chr15-50600917-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017672.6(TRPM7):c.2989-1621C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,108 control chromosomes in the GnomAD database, including 2,219 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2219 hom., cov: 32)

Consequence

TRPM7
NM_017672.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.51

Publications

3 publications found

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]

TRPM7 Gene-Disease associations (from GenCC):

hypomagnesemia, seizures, and intellectual disability
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
autosomal dominant macrothrombocytopenia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
macrothrombocytopenia, isolated
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
amyotrophic lateral sclerosis-parkinsonism-dementia complex
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TRPM7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM7	NM_017672.6 link	c.2989-1621C>A		intron_variant	Intron 21 of 38	ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1 link	c.2989-1621C>A		intron_variant	Intron 21 of 38		NM_017672.6	ENSP00000495860.1
TRPM7	ENST00000560955.5 link	c.2989-1621C>A		intron_variant	Intron 21 of 38	1		ENSP00000453277.1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22368

AN:

151990

Hom.:

2220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0434

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.147

AC:

22373

AN:

152108

Hom.:

2219

Cov.:

AF XY:

0.147

AC XY:

10966

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0435

AC:

1805

AN:

41518

American (AMR)

AF:

0.280

AC:

4283

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

794

AN:

3460

East Asian (EAS)

AF:

0.00290

AC:

AN:

5178

South Asian (SAS)

AF:

0.204

AC:

982

AN:

4818

European-Finnish (FIN)

AF:

0.131

AC:

1387

AN:

10566

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12558

AN:

67976

Other (OTH)

AF:

0.184

AC:

387

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

937

1873

2810

3746

4683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0604

Hom.:

Bravo

AF:

0.155

Asia WGS

AF:

0.0890

AC:

308

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.040

(source)

DANN

Benign

0.39

PhyloP100

-2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over