2-32666685-A-G

Position:

• chr2-32666685-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017735.5(TTC27):​c.856A>G​(p.Ile286Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: TTC27 NM_017735.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.71

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11369172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC27	NM_017735.5	c.856A>G	p.Ile286Val	missense_variant	7/20	ENST00000317907.9	NP_060205.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC27	ENST00000317907.9	c.856A>G	p.Ile286Val	missense_variant	7/20	1	NM_017735.5	ENSP00000313953	P1
TTC27	ENST00000647819.1	c.856A>G	p.Ile286Val	missense_variant, NMD_transcript_variant	7/22			ENSP00000497009
TTC27	ENST00000454690.1	c.89-12171A>G		intron_variant, NMD_transcript_variant		3		ENSP00000392883

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.856A>G (p.I286V) alteration is located in exon 7 (coding exon 7) of the TTC27 gene. This alteration results from a A to G substitution at nucleotide position 856, causing the isoleucine (I) at amino acid position 286 to be replaced by a valine (V). 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	0.091
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.91	L
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.034
Sift	Benign	0.59	T
Sift4G	Benign	0.87	T
Polyphen		0.025	B
Vest4		0.19
MutPred		0.40		Gain of helix (P = 0.2294);
MVP		0.45
MPC		0.036
ClinPred		0.81	D
GERP RS		4.6
Varity_R		0.061
gMVP		0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs1382552118; hg19: chr2-32891752;