chr6-11735569-G-T

Position:

• chr6-11735569-G-T

Variant summary

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

The NM_032744.4(ADTRP):​c.505C>A​(p.Arg169Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADTRP NM_032744.4 missense, splice_region
• Scores: Splicing: ADA: 0.00003660
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.37

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]

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	UniProt
ADTRP	NM_032744.4	c.505C>A	p.Arg169Ser	missense_variant, splice_region_variant	4/6	ENST00000414691.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADTRP	ENST00000414691.8	c.505C>A	p.Arg169Ser	missense_variant, splice_region_variant	4/6	1	NM_032744.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jan 31, 2024

The c.559C>A (p.R187S) 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 559, causing the arginine (R) at amino acid position 187 to be replaced by a serine (S). 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	Pathogenic	0.72
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.027	T;.;T
Eigen	Benign	-0.026
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.86	D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	M;.;.
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.54
MutPred		0.68		Gain of glycosylation at R169 (P = 0.0652);.;.;
MVP		0.29
MPC		0.53
ClinPred		0.97	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.64
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000037
dbscSNV1_RF	Benign	0.076
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-11735802;