6-11770074-C-G

Variant names:

• chr6-11770074-C-G
• rs1173320587
• NM_032744.4:c.154-1691G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001143948.2(ADTRP):​c.164G>C​(p.Arg55Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R55K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ADTRP NM_001143948.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.120408535).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143948.2. 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.154-1691G>C		intron	N/A	NP_116133.1	Q96IZ2-1
	ADTRP	NM_001143948.2		c.164G>C	p.Arg55Thr	missense	Exon 2 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.154-1691G>C		intron	N/A	ENSP00000404416.2	Q96IZ2-1
	ADTRP	ENST00000229583.9	TSL:2	c.164G>C	p.Arg55Thr	missense	Exon 2 of 7	ENSP00000229583.5	Q96IZ2-2
	ADTRP	ENST00000894491.1		c.154-1691G>C		intron	N/A	ENSP00000564550.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000649 AC: 1 AN: 154026 AF XY: 0.0000122

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399388 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690206

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.0000280 AC: 1 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078964

Other (OTH) AF: 0.00 AC: 0 AN: 58000

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.91
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.93	T
PhyloP100		0.43
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.040
Sift	Benign	0.087	T
Sift4G	Benign	0.11	T
Polyphen		0.19	B
Vest4		0.27
MutPred		0.62		Loss of MoRF binding (P = 0.0644)
MVP		0.061
MPC		0.34
ClinPred		0.099	T
GERP RS		-0.56
gMVP		0.36
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1173320587; hg19: chr6-11770307;