2-19901798-G-T

Position:

• chr2-19901798-G-T

Variant summary

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

The NM_001008237.3(TTC32):​c.57C>A​(p.Phe19Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TTC32 NM_001008237.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93

Genes affected

TTC32 (HGNC:32954): (tetratricopeptide repeat domain 32)

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=0.3629181).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC32	NM_001008237.3	c.57C>A	p.Phe19Leu	missense_variant	1/3	ENST00000333610.4	NP_001008238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC32	ENST00000333610.4	c.57C>A	p.Phe19Leu	missense_variant	1/3	1	NM_001008237.3	ENSP00000333018.3
TTC32	ENST00000402414.1	c.57C>A	p.Phe19Leu	missense_variant	1/2	5		ENSP00000385708.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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, 2022

The c.57C>A (p.F19L) alteration is located in exon 1 (coding exon 1) of the TTC32 gene. This alteration results from a C to A substitution at nucleotide position 57, causing the phenylalanine (F) at amino acid position 19 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	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.058	.;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.7	.;M
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-6.0	D;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;T
Sift4G	Pathogenic	0.0	D;T
Polyphen		0.018	.;B
Vest4		0.64
MutPred		0.42		Gain of disorder (P = 0.0487);Gain of disorder (P = 0.0487);
MVP		0.67
MPC		0.27
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.22
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-20101559;