Genetic Variant ADTRP:p.Val124Met (chr6-11766294-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032744.4(ADTRP):c.370G>A(p.Val124Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00028 in 1,611,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V124L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

ADTRP
NM_032744.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

7 publications found

Variant links:

Genes affected

ADTRP (HGNC:21214): (androgen dependent TFPI regulating protein) Enables hydrolase activity. Involved in several processes, including cell migration involved in sprouting angiogenesis; negative regulation of secretion by cell; and positive regulation of macromolecule metabolic process. Located in caveola and cell surface. [provided by Alliance of Genome Resources, Apr 2022]

ADTRP links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011869162).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032744.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADTRP	NM_032744.4	MANE Select	c.370G>A	p.Val124Met	missense	Exon 3 of 6	NP_116133.1	Q96IZ2-1
	ADTRP	NM_001143948.2		c.424G>A	p.Val142Met	missense	Exon 4 of 7	NP_001137420.1	Q96IZ2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADTRP	ENST00000414691.8	TSL:1 MANE Select	c.370G>A	p.Val124Met	missense	Exon 3 of 6	ENSP00000404416.2	Q96IZ2-1
ADTRP	ENST00000894491.1		c.520G>A	p.Val174Met	missense	Exon 4 of 7	ENSP00000564550.1
ADTRP	ENST00000229583.9	TSL:2	c.424G>A	p.Val142Met	missense	Exon 4 of 7	ENSP00000229583.5	Q96IZ2-2

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000436

AC:

109

AN:

249952

AF XY:

0.000355

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00475

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000280

AC:

409

AN:

1459180

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

195

AN XY:

725862

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33416

American (AMR)

AF:

0.0000225

AC:

AN:

44454

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00212

AC:

AN:

39590

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85724

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000267

AC:

297

AN:

1110578

Other (OTH)

AF:

0.000349

AC:

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000276

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41528

American (AMR)

AF:

0.000131

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00386

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000293

Hom.:

Bravo

AF:

0.000234

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000395

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.4

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0013

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.18

M_CAP

Benign

0.011

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

-1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.72

REVEL

Benign

0.063

Sift

Benign

0.049

Sift4G

Benign

0.094

Polyphen

0.70

Vest4

0.18

MVP

0.15

MPC

0.13

ClinPred

0.021

GERP RS

-0.29

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.048

gMVP

0.22

Mutation Taster

=90/10

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

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