6-11766294-C-G

Variant names:

• chr6-11766294-C-G
• rs76154682
• NM_032744.4:c.370G>C

Variant summary

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

The NM_032744.4(ADTRP):​c.370G>C​(p.Val124Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADTRP NM_032744.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 7 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=0.09288803).

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.370G>C	p.Val124Leu	missense	Exon 3 of 6	NP_116133.1	Q96IZ2-1
	ADTRP	NM_001143948.2		c.424G>C	p.Val142Leu	missense	Exon 4 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.370G>C	p.Val124Leu	missense	Exon 3 of 6	ENSP00000404416.2	Q96IZ2-1
	ADTRP	ENST00000894491.1		c.520G>C	p.Val174Leu	missense	Exon 4 of 7	ENSP00000564550.1
	ADTRP	ENST00000229583.9	TSL:2	c.424G>C	p.Val142Leu	missense	Exon 4 of 7	ENSP00000229583.5	Q96IZ2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.97
DANN	Benign	0.74
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		-1.0
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.083
Sift	Benign	0.12	T
Sift4G	Benign	0.25	T
Polyphen		0.030	B
Vest4		0.18
MutPred		0.41		Gain of helix (P = 0.1736)
MVP		0.10
MPC		0.12
ClinPred		0.11	T
GERP RS		-0.29
Varity_R		0.074
gMVP		0.26
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs76154682; hg19: chr6-11766527;