Variant 6-11714491-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.680A>G(p.Lys227Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,613,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ADTRP
NM_032744.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.276

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=0.044507504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADTRP	NM_032744.4 linkuse as main transcript	c.680A>G	p.Lys227Arg	missense_variant	6/6	ENST00000414691.8
ADTRP	NM_001143948.2 linkuse as main transcript	c.734A>G	p.Lys245Arg	missense_variant	7/7
ADTRP	XM_011514956.2 linkuse as main transcript	c.*18A>G		3_prime_UTR_variant	7/7
ADTRP	XM_047419420.1 linkuse as main transcript	c.*18A>G		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADTRP	ENST00000414691.8 linkuse as main transcript	c.680A>G	p.Lys227Arg	missense_variant	6/6	1	NM_032744.4	P1	Q96IZ2-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000176

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000137

AC:

AN:

248802

Hom.:

AF XY:

0.000134

AC XY:

AN XY:

134708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000287

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000137

AC:

200

AN:

1461546

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

103

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000167

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000125

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000123

Hom.:

Bravo

AF:

0.000144

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

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

Apr 18, 2023

The c.734A>G (p.K245R) alteration is located in exon 7 (coding exon 7) of the ADTRP gene. This alteration results from a A to G substitution at nucleotide position 734, causing the lysine (K) at amino acid position 245 to be replaced by an arginine (R). 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

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.2

DANN

Benign

0.96

DEOGEN2

Benign

0.0018

T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.89

N;N

REVEL

Benign

0.020

Sift

Benign

0.62

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.93

P;B

Vest4

0.043

MVP

0.32

MPC

0.098

ClinPred

0.017

GERP RS

1.9

Varity_R

0.047

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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