1-156581477-C-T

Variant names:

• chr1-156581477-C-T
• NM_001105669.4:c.113C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001105669.4(TTC24):​c.113C>T​(p.Ala38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A38T) has been classified 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: 0.0170
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057677686).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105669.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC24	NM_001105669.4	MANE Select	c.113C>T	p.Ala38Val	missense	Exon 2 of 11	NP_001099139.2	A2A3L6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC24	ENST00000368236.8	TSL:5 MANE Select	c.113C>T	p.Ala38Val	missense	Exon 2 of 11	ENSP00000357219.3	A2A3L6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399008 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 689962

African (AFR) AF: 0.00 AC: 0 AN: 31576

American (AMR) AF: 0.00 AC: 0 AN: 35654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25162

East Asian (EAS) AF: 0.00 AC: 0 AN: 35728

South Asian (SAS) AF: 0.00 AC: 0 AN: 79210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078746

Other (OTH) AF: 0.0000173 AC: 1 AN: 57970

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.017
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.073
Sift	Benign	0.26	T
Sift4G	Benign	0.14	T
Vest4		0.065
MutPred		0.37		Loss of helix (P = 0.0376)
MVP		0.27
MPC		0.11
ClinPred		0.087	T
GERP RS		0.15
Varity_R		0.044
gMVP		0.16
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

hg19: chr1-156551269;