2-19901776-C-A

Position:

• chr2-19901776-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001008237.3(TTC32):​c.79G>T​(p.Ala27Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TTC32 NM_001008237.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.34

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC32	NM_001008237.3	c.79G>T	p.Ala27Ser	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.79G>T	p.Ala27Ser	missense_variant	1/3	1	NM_001008237.3	ENSP00000333018.3
TTC32	ENST00000402414.1	c.79G>T	p.Ala27Ser	missense_variant	1/2	5		ENSP00000385708.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251318 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135836

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461844 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

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

Aug 12, 2022

The c.79G>T (p.A27S) alteration is located in exon 1 (coding exon 1) of the TTC32 gene. This alteration results from a G to T substitution at nucleotide position 79, causing the alanine (A) at amino acid position 27 to be replaced by a serine (S). 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	0.27
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.78	T;T
M_CAP	Pathogenic	0.43	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Pathogenic	0.85	D
MutationAssessor	Uncertain	2.7	.;M
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.0	D;N
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;T
Polyphen		1.0	.;D
Vest4		0.54
MutPred		0.61		Gain of disorder (P = 0.0567);Gain of disorder (P = 0.0567);
MVP		0.95
MPC		0.25
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.39
gMVP		0.62

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: rs776881771; hg19: chr2-20101537;