Variant 6-11770075-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032744.4(ADTRP):c.154-1692A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,551,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ADTRP
NM_032744.4 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.673

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055963665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADTRP	NM_032744.4 linkuse as main transcript	c.154-1692A>G		intron_variant		ENST00000414691.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADTRP	ENST00000414691.8 linkuse as main transcript	c.154-1692A>G		intron_variant		1	NM_032744.4	P1	Q96IZ2-1

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000970

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000156

AC:

AN:

153996

Hom.:

AF XY:

0.0000979

AC XY:

AN XY:

81720

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000335

Gnomad OTH exome

AF:

0.000692

GnomAD4 exome

AF:

0.000170

AC:

238

AN:

1399384

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

105

AN XY:

690200

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000214

Gnomad4 OTH exome

AF:

0.0000690

GnomAD4 genome

AF:

0.000132

AC:

AN:

151924

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.0000968

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000276

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.163A>G (p.R55G) alteration is located in exon 2 (coding exon 2) of the ADTRP gene. This alteration results from a A to G substitution at nucleotide position 163, causing the arginine (R) at amino acid position 55 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.7

DANN

Uncertain

0.98

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.31

M_CAP

Benign

0.0064

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

0.39

REVEL

Benign

0.028

Sift

Benign

0.059

Sift4G

Benign

0.075

Polyphen

0.19

Vest4

0.23

MutPred

0.51

Gain of relative solvent accessibility (P = 0.0098);

MVP

0.088

MPC

0.26

ClinPred

0.039

GERP RS

-2.3

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over