2-19901776-C-T

Variant names:

• chr2-19901776-C-T
• rs776881771
• NM_001008237.3:c.79G>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>A​(p.Ala27Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A27S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TTC32 NM_001008237.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34

Genes affected

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

TTC32-DT (HGNC:55236): (TTC32 divergent transcript)

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, 0.836

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC32	NM_001008237.3	c.79G>A	p.Ala27Thr	missense_variant	Exon 1 of 3	ENST00000333610.4	NP_001008238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC32	ENST00000333610.4	c.79G>A	p.Ala27Thr	missense_variant	Exon 1 of 3	1	NM_001008237.3	ENSP00000333018.3
TTC32	ENST00000402414.1	c.79G>A	p.Ala27Thr	missense_variant	Exon 1 of 2	5		ENSP00000385708.1
TTC32	ENST00000431392.1	c.-655G>A		upstream_gene_variant		3		ENSP00000412874.1
TTC32-DT	ENST00000607190.2	n.-246C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251318 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135836

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461844 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	.;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.81	T;T
M_CAP	Pathogenic	0.46	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Uncertain	2.7	.;M
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-4.0	D;N
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.56
MutPred		0.59		Gain of phosphorylation at A27 (P = 0.0707);Gain of phosphorylation at A27 (P = 0.0707);
MVP		0.96
MPC		0.26
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.36
gMVP		0.74

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; COSMIC: COSV61267359; COSMIC: COSV61267359;