12-49325801-C-G

Variant names:

• chr12-49325801-C-G
• rs140223921
• NM_005480.4:c.550C>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.550C>G​(p.Pro184Ala) 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. 13/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P184S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TROAP NM_005480.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.942
• Publications: 2 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]

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=0.20203319).

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.550C>G	p.Pro184Ala	missense	Exon 5 of 15	NP_005471.3
	TROAP	NM_001410976.1		c.550C>G	p.Pro184Ala	missense	Exon 5 of 14	NP_001397905.1	F8W130

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TROAP	ENST00000257909.8	TSL:1 MANE Select	c.550C>G	p.Pro184Ala	missense	Exon 5 of 15	ENSP00000257909.3	Q12815-1
	TROAP	ENST00000546735.5	TSL:1	n.*195C>G		non_coding_transcript_exon	Exon 4 of 10	ENSP00000447876.1	F8VR46
	TROAP	ENST00000546735.5	TSL:1	n.*195C>G		3_prime_UTR	Exon 4 of 10	ENSP00000447876.1	F8VR46

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251022 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.94
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.024	D
Polyphen		0.95	P
Vest4		0.67
MutPred		0.41		Loss of loop (P = 0.0075)
MVP		0.32
MPC		0.68
ClinPred		0.98	D
GERP RS		3.1
Varity_R		0.46
gMVP		0.049
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs140223921; hg19: chr12-49719584;