2-32633895-C-T

Variant names:

• chr2-32633895-C-T
• NM_017735.5:c.286C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017735.5(TTC27):​c.286C>T​(p.Leu96Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000014 (0 hom.)
• Consequence: TTC27 NM_017735.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34483266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC27	NM_017735.5	c.286C>T	p.Leu96Phe	missense_variant	Exon 3 of 20	ENST00000317907.9	NP_060205.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC27	ENST00000317907.9	c.286C>T	p.Leu96Phe	missense_variant	Exon 3 of 20	1	NM_017735.5	ENSP00000313953.4
TTC27	ENST00000448773.5	c.136C>T	p.Leu46Phe	missense_variant	Exon 3 of 4	4		ENSP00000393327.1
TTC27	ENST00000647819.1	n.286C>T		non_coding_transcript_exon_variant	Exon 3 of 22			ENSP00000497009.1
TTC27	ENST00000454690.1	n.88+5515C>T		intron_variant	Intron 1 of 3	3		ENSP00000392883.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461548 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727052

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.286C>T (p.L96F) alteration is located in exon 3 (coding exon 3) of the TTC27 gene. This alteration results from a C to T substitution at nucleotide position 286, causing the leucine (L) at amino acid position 96 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	.;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.072
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.025	D;D
Polyphen		0.79	.;P
Vest4		0.51
MutPred		0.46		.;Loss of helix (P = 0.0795);
MVP		0.79
MPC		0.079
ClinPred		0.93	D
GERP RS		3.7
Varity_R		0.11
gMVP		0.52

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-32858962; COSMIC: COSV58651869; COSMIC: COSV58651869;