2-32664336-C-G

Variant names:

• chr2-32664336-C-G
• rs1055909446
• NM_017735.5:c.674C>G

Variant summary

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

The NM_017735.5(TTC27):​c.674C>G​(p.Ser225*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC27 NM_017735.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 0 publications found

Genes affected

TTC27 (HGNC:25986): (tetratricopeptide repeat domain 27)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017735.5. 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
	TTC27	NM_017735.5	MANE Select	c.674C>G	p.Ser225*	stop_gained	Exon 6 of 20	NP_060205.3
	TTC27	NM_001193509.2		c.524C>G	p.Ser175*	stop_gained	Exon 6 of 20	NP_001180438.1	B4DRC7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC27	ENST00000317907.9	TSL:1 MANE Select	c.674C>G	p.Ser225*	stop_gained	Exon 6 of 20	ENSP00000313953.4	Q6P3X3
	TTC27	ENST00000934659.1		c.674C>G	p.Ser225*	stop_gained	Exon 6 of 20	ENSP00000604718.1
	TTC27	ENST00000956005.1		c.674C>G	p.Ser225*	stop_gained	Exon 6 of 20	ENSP00000626064.1

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
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.45	N
PhyloP100		2.0
Vest4		0.30
GERP RS		3.9
Mutation Taster		=9/191	disease causing (fs/PTC)

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: rs1055909446; hg19: chr2-32889403;