chr12-49324032-A-G

Variant names:

• chr12-49324032-A-G
• NM_005480.4:c.332A>G

Variant summary

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

The NM_005480.4(TROAP):​c.332A>G​(p.Gln111Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TROAP NM_005480.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.153
• Publications: 0 publications found

Genes affected

TROAP (HGNC:12327): (trophinin associated protein) Predicted to be involved in cell adhesion. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TROAP-AS1 (HGNC:55453): (TROAP and PRPH antisense RNA 1)

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=0.0806503).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005480.4. 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
	TROAP	NM_005480.4	MANE Select	c.332A>G	p.Gln111Arg	missense	Exon 3 of 15	NP_005471.3
	TROAP	NM_001410976.1		c.332A>G	p.Gln111Arg	missense	Exon 3 of 14	NP_001397905.1	F8W130
	TROAP	NM_001100620.3		c.332A>G	p.Gln111Arg	missense	Exon 3 of 4	NP_001094090.1	Q12815-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TROAP	ENST00000257909.8	TSL:1 MANE Select	c.332A>G	p.Gln111Arg	missense	Exon 3 of 15	ENSP00000257909.3	Q12815-1
	TROAP	ENST00000380327.9	TSL:1	c.332A>G	p.Gln111Arg	missense	Exon 3 of 4	ENSP00000369684.5	Q12815-2
	TROAP	ENST00000546735.5	TSL:1	n.144+280A>G		intron	N/A	ENSP00000447876.1	F8VR46

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460740 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726618

African (AFR) AF: 0.00 AC: 0 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111308

Other (OTH) AF: 0.00 AC: 0 AN: 60352

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	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Uncertain	0.97
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PhyloP100		0.15
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.026
Sift	Benign	0.10	T
Sift4G	Benign	0.31	T
Polyphen		0.013	B
Vest4		0.26
MutPred		0.14		Loss of glycosylation at P115 (P = 0.2465)
MVP		0.20
MPC		0.20
ClinPred		0.10	T
GERP RS		1.9
Varity_R		0.072
gMVP		0.063
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr12-49717815;