NM_005480.4:c.550C>A

Variant names:

• chr12-49325801-C-A
• rs140223921
• NM_005480.4:c.550C>A

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>A​(p.Pro184Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TROAP NM_005480.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.942
• 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]

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=0.23063934).

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>A	p.Pro184Thr	missense	Exon 5 of 15	NP_005471.3
	TROAP	NM_001410976.1		c.550C>A	p.Pro184Thr	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>A	p.Pro184Thr	missense	Exon 5 of 15	ENSP00000257909.3	Q12815-1
	TROAP	ENST00000546735.5	TSL:1	n.*195C>A		non_coding_transcript_exon	Exon 4 of 10	ENSP00000447876.1	F8VR46
	TROAP	ENST00000546735.5	TSL:1	n.*195C>A		3_prime_UTR	Exon 4 of 10	ENSP00000447876.1	F8VR46

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461814 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.94
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.23	T
Polyphen		0.98	D
Vest4		0.83
MutPred		0.41		Gain of phosphorylation at P184 (P = 0.045)
MVP		0.32
MPC		0.75
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.63
gMVP		0.098
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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;