1-156581752-C-T

Variant names:

• chr1-156581752-C-T
• NM_001105669.4:c.388C>T

Variant summary

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

The NM_001105669.4(TTC24):​c.388C>T​(p.Leu130Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,348 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TTC24 NM_001105669.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.72

Genes affected

TTC24 (HGNC:32348): (tetratricopeptide repeat domain 24)

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 rank	MANE	Protein	UniProt
TTC24	NM_001105669.4	c.388C>T	p.Leu130Phe	missense_variant	Exon 2 of 11	ENST00000368236.8	NP_001099139.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC24	ENST00000368236.8	c.388C>T	p.Leu130Phe	missense_variant	Exon 2 of 11	5	NM_001105669.4	ENSP00000357219.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399348 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690180

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.388C>T (p.L130F) alteration is located in exon 2 (coding exon 1) of the TTC24 gene. This alteration results from a C to T substitution at nucleotide position 388, causing the leucine (L) at amino acid position 130 to be replaced by a phenylalanine (F). 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	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T;T
Eigen	Benign	0.055
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.63	T;.
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.26
Sift	Uncertain	0.010	D;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.61
MutPred		0.42		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP		0.56
MPC		0.52
ClinPred		0.97	D
GERP RS		3.7
Varity_R		0.20
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-156551544;