6-11735569-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032744.4(ADTRP):​c.505C>T​(p.Arg169Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000615 in 1,608,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R169S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: ADTRP NM_032744.4 missense, splice_region
• Scores: Splicing: ADA: 0.0002495
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19489914).

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>T	p.Arg169Cys	missense splice_region	Exon 4 of 6	NP_116133.1	Q96IZ2-1
	ADTRP	NM_001143948.2		c.559C>T	p.Arg187Cys	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>T	p.Arg169Cys	missense splice_region	Exon 4 of 6	ENSP00000404416.2	Q96IZ2-1
	ADTRP	ENST00000894491.1		c.655C>T	p.Arg219Cys	missense splice_region	Exon 5 of 7	ENSP00000564550.1
	ADTRP	ENST00000229583.9	TSL:2	c.559C>T	p.Arg187Cys	missense splice_region	Exon 5 of 7	ENSP00000229583.5	Q96IZ2-2

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000679 AC: 17 AN: 250466 AF XY: 0.0000665

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000320

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000583 AC: 85 AN: 1456756 Hom.: 0 Cov.: 30 AF XY: 0.0000593 AC XY: 43 AN XY: 724962

African (AFR) AF: 0.0000300 AC: 1 AN: 33376

American (AMR) AF: 0.000448 AC: 20 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000497 AC: 55 AN: 1107640

Other (OTH) AF: 0.000133 AC: 8 AN: 60244

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74324

African (AFR) AF: 0.0000483 AC: 2 AN: 41446

American (AMR) AF: 0.000196 AC: 3 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68042

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.0000914 Hom.: 0

Bravo AF: 0.0000982

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.00

EpiControl AF: 0.0000595

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	Benign	0.33
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.040
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.4
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.26
Sift	Benign	0.13	T
Sift4G	Benign	0.068	T
Polyphen		1.0	D
Vest4		0.43
MVP		0.29
MPC		0.64
ClinPred		0.45	T
GERP RS		2.5
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.72
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00025
dbscSNV1_RF	Benign	0.060
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

Other links and lift over

dbSNP: rs369600337; hg19: chr6-11735802; COSMIC: COSV105851461; COSMIC: COSV105851461;