7-142871843-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018646.6(TRPV6):c.2162T>C(p.Met721Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 1,613,972 control chromosomes in the GnomAD database, including 15,697 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 6414 hom., cov: 33)

Exomes 𝑓: 0.083 ( 9283 hom. )

Consequence

TRPV6
NM_018646.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.13

Publications

28 publications found

Variant links:

Genes affected

TRPV6 (HGNC:14006): (transient receptor potential cation channel subfamily V member 6) This gene encodes a member of a family of multipass membrane proteins that functions as calcium channels. The encoded protein contains N-terminal ankyrin repeats, which are required for channel assembly and regulation. Translation initiation for this protein occurs at a non-AUG start codon that is decoded as methionine. This gene is situated next to a closely related gene for transient receptor potential cation channel subfamily V member 5 (TRPV5). This locus has experienced positive selection in non-African populations, resulting in several non-synonymous codon differences among individuals of different genetic backgrounds. [provided by RefSeq, Feb 2015]

TRPV6 Gene-Disease associations (from GenCC):

hyperparathyroidism, transient neonatal
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P
intestinal hypomagnesemia 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
pancreatitis
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
neonatal severe primary hyperparathyroidism
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TRPV6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.153571E-5).

BP6

Variant 7-142871843-A-G is Benign according to our data. Variant chr7-142871843-A-G is described in ClinVar as Benign. ClinVar VariationId is 2786649.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018646.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV6	NM_018646.6	MANE Select	c.2162T>C	p.Met721Thr	missense	Exon 15 of 15	NP_061116.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TRPV6	ENST00000359396.9	TSL:1 MANE Select	c.2162T>C	p.Met721Thr	missense	Exon 15 of 15	ENSP00000352358.5
TRPV6	ENST00000485138.5	TSL:2	n.1772T>C		non_coding_transcript_exon	Exon 9 of 9
TRPV6	ENST00000615386.4	TSL:2	n.9803T>C		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30573

AN:

151994

Hom.:

6395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.536

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0648

Gnomad EAS

AF:

0.0212

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0728

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0768

Gnomad OTH

AF:

0.181

GnomAD2 exomes

AF:

0.0919

AC:

23113

AN:

251440

AF XY:

0.0800

show subpopulations

Gnomad AFR exome

AF:

0.548

Gnomad AMR exome

AF:

0.0561

Gnomad ASJ exome

AF:

0.0610

Gnomad EAS exome

AF:

0.0202

Gnomad FIN exome

AF:

0.0779

Gnomad NFE exome

AF:

0.0766

Gnomad OTH exome

AF:

0.0830

GnomAD4 exome

AF:

0.0834

AC:

121926

AN:

1461860

Hom.:

9283

Cov.:

AF XY:

0.0793

AC XY:

57702

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.550

AC:

18416

AN:

33478

American (AMR)

AF:

0.0598

AC:

2674

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0603

AC:

1577

AN:

26136

East Asian (EAS)

AF:

0.0143

AC:

569

AN:

39700

South Asian (SAS)

AF:

0.0123

AC:

1060

AN:

86256

European-Finnish (FIN)

AF:

0.0788

AC:

4208

AN:

53414

Middle Eastern (MID)

AF:

0.0799

AC:

461

AN:

5768

European-Non Finnish (NFE)

AF:

0.0782

AC:

86974

AN:

1111994

Other (OTH)

AF:

0.0991

AC:

5987

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

6554

13108

19663

26217

32771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3366

6732

10098

13464

16830

<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:

0.201

AC:

30636

AN:

152112

Hom.:

6414

Cov.:

AF XY:

0.193

AC XY:

14364

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.536

AC:

22240

AN:

41460

American (AMR)

AF:

0.102

AC:

1565

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0648

AC:

225

AN:

3470

East Asian (EAS)

AF:

0.0213

AC:

110

AN:

5170

South Asian (SAS)

AF:

0.0120

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0728

AC:

772

AN:

10598

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0768

AC:

5223

AN:

67988

Other (OTH)

AF:

0.179

AC:

378

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

919

1838

2756

3675

4594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.123

Hom.:

7325

Bravo

AF:

0.220

TwinsUK

AF:

0.0820

AC:

304

ALSPAC

AF:

0.0747

AC:

288

ESP6500AA

AF:

0.530

AC:

2336

ESP6500EA

AF:

0.0787

AC:

677

ExAC

AF:

0.101

AC:

12225

Asia WGS

AF:

0.0570

AC:

198

AN:

3478

EpiCase

AF:

0.0748

EpiControl

AF:

0.0788

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

TRPV6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.60

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.16

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00046

LIST_S2

Benign

0.0069

MetaRNN

Benign

0.000072

MetaSVM

Benign

-0.95

PhyloP100

1.1

PrimateAI

Benign

0.32

REVEL

Benign

0.042

Sift4G

Benign

0.61

Vest4

0.012

MPC

0.32

ClinPred

0.00078

GERP RS

1.3

Varity_R

0.088

gMVP

0.21

Mutation Taster

=97/3

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

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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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over