6-11735569-G-T

Variant names:

• chr6-11735569-G-T
• rs369600337
• NM_032744.4:c.505C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R169C) has been classified 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.505C>A	p.Arg169Ser	missense splice_region	Exon 4 of 6	NP_116133.1	Q96IZ2-1
	ADTRP	NM_001143948.2		c.559C>A	p.Arg187Ser	missense splice_region	Exon 5 of 7	NP_001137420.1	Q96IZ2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADTRP	ENST00000414691.8	TSL:1 MANE Select	c.505C>A	p.Arg169Ser	missense splice_region	Exon 4 of 6	ENSP00000404416.2	Q96IZ2-1
	ADTRP	ENST00000894491.1		c.655C>A	p.Arg219Ser	missense splice_region	Exon 5 of 7	ENSP00000564550.1
	ADTRP	ENST00000229583.9	TSL:2	c.559C>A	p.Arg187Ser	missense splice_region	Exon 5 of 7	ENSP00000229583.5	Q96IZ2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.026
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.4
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.30
Sift	Benign	0.21	T
Sift4G	Benign	0.21	T
Polyphen		1.0	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
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.64
gMVP		0.75
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs369600337; hg19: chr6-11735802;