5-40716429-A-G

Variant summary

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

The NM_012382.3(TTC33):c.505T>C(p.Ser169Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,500 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TTC33 NM_012382.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45

Genes affected

TTC33 (HGNC:29959): (tetratricopeptide repeat domain 33)

PTGER4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC33	NM_012382.3	c.505T>C	p.Ser169Pro	missense_variant	5/5	ENST00000337702.5
TTC33	XM_011514003.4	c.505T>C	p.Ser169Pro	missense_variant	5/5
PTGER4	XM_017009659.3	c.*37+19666A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC33	ENST00000337702.5	c.505T>C	p.Ser169Pro	missense_variant	5/5	1	NM_012382.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461500 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727012

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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 23, 2024

The c.505T>C (p.S169P) alteration is located in exon 5 (coding exon 4) of the TTC33 gene. This alteration results from a T to C substitution at nucleotide position 505, causing the serine (S) at amino acid position 169 to be replaced by a proline (P). 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	0.61
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0094	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.18
Sift	Uncertain	0.019	D
Sift4G	Benign	0.072	T
Polyphen		0.99	D
Vest4		0.74
MutPred		0.52		Loss of MoRF binding (P = 0.0605);
MVP		0.41
MPC		0.23
ClinPred		0.66	D
GERP RS		5.8
Varity_R		0.51
gMVP		0.82

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: chr5-40716531;