6-11735637-G-T

Position:

• chr6-11735637-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032744.4(ADTRP):​c.437C>A​(p.Pro146His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADTRP NM_032744.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.61

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADTRP	NM_032744.4	c.437C>A	p.Pro146His	missense_variant	4/6	ENST00000414691.8	NP_116133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADTRP	ENST00000414691.8	c.437C>A	p.Pro146His	missense_variant	4/6	1	NM_032744.4	ENSP00000404416.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 08, 2024

The c.491C>A (p.P164H) alteration is located in exon 5 (coding exon 5) of the ADTRP gene. This alteration results from a C to A substitution at nucleotide position 491, causing the proline (P) at amino acid position 164 to be replaced by a histidine (H). 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	0.29
BayesDel_addAF	Benign	0.0074	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Benign	0.83
DEOGEN2	Benign	0.0044	T;.;T;.;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.048
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.75	T;T;T;.;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.46	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.7	D;D;D;N;N
REVEL	Benign	0.21
Sift	Benign	0.54	T;T;T;T;T
Sift4G	Benign	0.39	T;T;D;.;T
Polyphen		1.0	D;D;.;.;.
Vest4		0.75
MVP		0.35
MPC		0.61
ClinPred		0.59	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.59

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

LitVar

Other links and lift over

dbSNP: rs377752092; hg19: chr6-11735870;