dbSNP rs473357: TRPM7:p.Tyr1662Tyr (chr15-50574885-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017672.6(TRPM7):c.4986C>T(p.Tyr1662Tyr) 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.07

Publications

29 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
macrothrombocytopenia, isolated
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
autosomal dominant macrothrombocytopenia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 15-50574885-G-A is Benign according to our data. Variant chr15-50574885-G-A is described in ClinVar as Benign. ClinVar VariationId is 1256704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017672.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRPM7	NM_017672.6	MANE Select	c.4986C>T	p.Tyr1662Tyr	synonymous	Exon 34 of 39	NP_060142.3
TRPM7	NM_001301212.2		c.4983C>T	p.Tyr1661Tyr	synonymous	Exon 34 of 39	NP_001288141.1	H0YLN8
TRPM7	NR_149152.2		n.5200C>T		non_coding_transcript_exon	Exon 34 of 39

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRPM7	ENST00000646667.1	MANE Select	c.4986C>T	p.Tyr1662Tyr	synonymous	Exon 34 of 39	ENSP00000495860.1	Q96QT4
TRPM7	ENST00000560955.5	TSL:1	c.4983C>T	p.Tyr1661Tyr	synonymous	Exon 34 of 39	ENSP00000453277.1	H0YLN8
TRPM7	ENST00000561267.5	TSL:3	c.123C>T	p.Tyr41Tyr	synonymous	Exon 1 of 6	ENSP00000454066.1	H0YNM0

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89712

AN:

151942

Hom.:

26777

Cov.:

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

GnomAD2 exomes

AF:

0.570

AC:

141859

AN:

248956

AF XY:

0.569

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 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.:

AF XY:

0.560

AC XY:

406343

AN XY:

725754

show subpopulations

African (AFR)

AF:

0.670

AC:

22349

AN:

33344

American (AMR)

AF:

0.621

AC:

27744

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.551

AC:

14361

AN:

26072

East Asian (EAS)

AF:

0.558

AC:

22141

AN:

39666

South Asian (SAS)

AF:

0.573

AC:

49387

AN:

86164

European-Finnish (FIN)

AF:

0.480

AC:

25630

AN:

53364

Middle Eastern (MID)

AF:

0.590

AC:

3403

AN:

5764

European-Non Finnish (NFE)

AF:

0.555

AC:

616110

AN:

1109230

Other (OTH)

AF:

0.565

AC:

34036

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

16558

33116

49674

66232

82790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17268

34536

51804

69072

86340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.590

AC:

89785

AN:

152062

Hom.:

26797

Cov.:

AF XY:

0.589

AC XY:

43804

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.665

AC:

27608

AN:

41492

American (AMR)

AF:

0.632

AC:

9654

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.555

AC:

1925

AN:

3470

East Asian (EAS)

AF:

0.570

AC:

2955

AN:

5182

South Asian (SAS)

AF:

0.560

AC:

2704

AN:

4826

European-Finnish (FIN)

AF:

0.475

AC:

5004

AN:

10542

Middle Eastern (MID)

AF:

0.613

AC:

179

AN:

292

European-Non Finnish (NFE)

AF:

0.558

AC:

37913

AN:

67956

Other (OTH)

AF:

0.611

AC:

1288

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1917

3833

5750

7666

9583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<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:

0.569

Hom.:

25527

Bravo

AF:

0.605

Asia WGS

AF:

0.561

AC:

1950

AN:

3478

EpiCase

AF:

0.580

EpiControl

AF:

0.583

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.2

(source)

DANN

Benign

0.52

PhyloP100

2.1

PromoterAI

-0.0042

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over