2-32664336-C-T

Variant names:

• chr2-32664336-C-T
• rs1055909446
• NM_017735.5:c.674C>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.674C>T​(p.Ser225Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 6.9e-7 (0 hom.)
• Consequence: TTC27 NM_017735.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10615468).

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>T	p.Ser225Leu	missense	Exon 6 of 20	NP_060205.3
	TTC27	NM_001193509.2		c.524C>T	p.Ser175Leu	missense	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>T	p.Ser225Leu	missense	Exon 6 of 20	ENSP00000313953.4	Q6P3X3
	TTC27	ENST00000934659.1		c.674C>T	p.Ser225Leu	missense	Exon 6 of 20	ENSP00000604718.1
	TTC27	ENST00000956005.1		c.674C>T	p.Ser225Leu	missense	Exon 6 of 20	ENSP00000626064.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455626 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723384

African (AFR) AF: 0.00 AC: 0 AN: 33280

American (AMR) AF: 0.00 AC: 0 AN: 43814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39442

South Asian (SAS) AF: 0.00 AC: 0 AN: 85104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108792

Other (OTH) AF: 0.00 AC: 0 AN: 60170

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	0.085
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.0
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.067
Sift	Benign	0.41	T
Sift4G	Benign	0.79	T
Polyphen		0.0060	B
Vest4		0.24
MutPred		0.45		Loss of loop (P = 0.0374)
MVP		0.45
MPC		0.037
ClinPred		0.14	T
GERP RS		3.9
Varity_R		0.064
gMVP		0.21
Mutation Taster		=86/14	polymorphism

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; COSMIC: COSV58651640;