2-32633977-C-T

Variant names:

• chr2-32633977-C-T
• NM_017735.5:c.368C>T

Variant summary

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

The NM_017735.5(TTC27):​c.368C>T​(p.Ser123Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S123P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTC27 NM_017735.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.66
• Publications: 0 publications found

Genes affected

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

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=0.22405571).

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.368C>T	p.Ser123Leu	missense	Exon 3 of 20	NP_060205.3
	TTC27	NM_001193509.2		c.218C>T	p.Ser73Leu	missense	Exon 3 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.368C>T	p.Ser123Leu	missense	Exon 3 of 20	ENSP00000313953.4	Q6P3X3
	TTC27	ENST00000934659.1		c.368C>T	p.Ser123Leu	missense	Exon 3 of 20	ENSP00000604718.1
	TTC27	ENST00000956005.1		c.368C>T	p.Ser123Leu	missense	Exon 3 of 20	ENSP00000626064.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.081
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.057
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		5.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.074
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.0080	B
Vest4		0.36
MutPred		0.48		Loss of loop (P = 0.0512)
MVP		0.77
MPC		0.037
ClinPred		0.78	D
GERP RS		5.5
Varity_R		0.074
gMVP		0.42
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: chr2-32859044;