chr15-50574892-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_017672.6(TRPM7):c.4979G>A(p.Ser1660Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000734 in 1,613,430 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0039 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00041 ( 4 hom. )

Consequence

TRPM7
NM_017672.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.54

Publications

4 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: Ambry Genetics, ClinGen
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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007270187).

BP6

Variant 15-50574892-C-T is Benign according to our data. Variant chr15-50574892-C-T is described in ClinVar as Benign. ClinVar VariationId is 3037491.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 588 Unknown,AD gene.

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.4979G>A	p.Ser1660Asn	missense	Exon 34 of 39	NP_060142.3
TRPM7	NM_001301212.2		c.4976G>A	p.Ser1659Asn	missense	Exon 34 of 39	NP_001288141.1	H0YLN8
TRPM7	NR_149152.2		n.5193G>A		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.4979G>A	p.Ser1660Asn	missense	Exon 34 of 39	ENSP00000495860.1	Q96QT4
TRPM7	ENST00000560955.5	TSL:1	c.4976G>A	p.Ser1659Asn	missense	Exon 34 of 39	ENSP00000453277.1	H0YLN8
TRPM7	ENST00000561267.5	TSL:3	c.116G>A	p.Ser39Asn	missense	Exon 1 of 6	ENSP00000454066.1	H0YNM0

Frequencies

GnomAD3 genomes

AF:

0.00383

AC:

583

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000983

AC:

245

AN:

249184

AF XY:

0.000747

show subpopulations

Gnomad AFR exome

AF:

0.0136

Gnomad AMR exome

AF:

0.000725

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000409

AC:

597

AN:

1461158

Hom.:

Cov.:

AF XY:

0.000355

AC XY:

258

AN XY:

726920

show subpopulations

African (AFR)

AF:

0.0133

AC:

446

AN:

33444

American (AMR)

AF:

0.000716

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000306

AC:

AN:

1111492

Other (OTH)

AF:

0.00124

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

126

158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00386

AC:

588

AN:

152272

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

288

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0134

AC:

557

AN:

41554

American (AMR)

AF:

0.00144

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68024

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

118

148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00143

Hom.:

Bravo

AF:

0.00447

ESP6500AA

AF:

0.0114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00119

AC:

144

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

TRPM7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

Eigen

Benign

-0.16

Eigen_PC

Benign

0.0078

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0073

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.77

PhyloP100

2.5

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.57

REVEL

Benign

0.073

Sift

Benign

0.12

Sift4G

Benign

0.079

Polyphen

0.0

Vest4

0.14

MVP

0.23

MPC

0.11

ClinPred

0.012

GERP RS

3.5

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.090

gMVP

0.51

Mutation Taster

=94/6

polymorphism

(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

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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