2-32633977-C-T

Position:

• chr2-32633977-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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: 5.66

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=0.22405571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC27	NM_017735.5	c.368C>T	p.Ser123Leu	missense_variant	3/20	ENST00000317907.9	NP_060205.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC27	ENST00000317907.9	c.368C>T	p.Ser123Leu	missense_variant	3/20	1	NM_017735.5	ENSP00000313953	P1
TTC27	ENST00000448773.5	c.218C>T	p.Ser73Leu	missense_variant	3/4	4		ENSP00000393327
TTC27	ENST00000647819.1	c.368C>T	p.Ser123Leu	missense_variant, NMD_transcript_variant	3/22			ENSP00000497009
TTC27	ENST00000454690.1	c.88+5597C>T		intron_variant, NMD_transcript_variant		3		ENSP00000392883

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jan 27, 2022

The c.368C>T (p.S123L) 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 368, causing the serine (S) at amino acid position 123 to be replaced by a leucine (L). 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	0.081
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;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	.;N
MutationTaster	Benign	0.96	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.97	N;N
REVEL	Benign	0.074
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0070	D;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-32859044;