rs1057516047

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate

The NM_020458.4(TTC7A):​c.2470C>T​(p.Gln824*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

TTC7A
NM_020458.4 stop_gained

Scores

5
1
1

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 6.15
Variant links:
Genes affected
TTC7A (HGNC:19750): (tetratricopeptide repeat domain 7A) This gene encodes a protein containing tetratricopeptide repeats. Mutations in this gene disrupt intestinal development and can cause early onset inflammatory bowel disease and intestinal atresia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0415 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-47073816-C-T is Pathogenic according to our data. Variant chr2-47073816-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 369683.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TTC7ANM_020458.4 linkuse as main transcriptc.2470C>T p.Gln824* stop_gained 20/20 ENST00000319190.11 NP_065191.2 Q9ULT0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TTC7AENST00000319190.11 linkuse as main transcriptc.2470C>T p.Gln824* stop_gained 20/202 NM_020458.4 ENSP00000316699.5 Q9ULT0-1
ENSG00000273269ENST00000422269.1 linkuse as main transcriptn.*656-7679G>A intron_variant 2 ENSP00000476793.1 V9GYI7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Multiple gastrointestinal atresias Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingVictorian Clinical Genetics Services, Murdoch Childrens Research InstituteSep 17, 2015This substitution is predicted to result in a premature stop codon at amino acid position 824, NP_065191.2: p.(Gln824*). In-silico software (MutationTaster) predicts this variant to be disease-causing. This is a novel variant, not previously reported in disease or population databases. It was identified in a homozygous state in an infant with multiple intestinal atresias. Both parents were confirmed to be carriers. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.61
D
BayesDel_noAF
Pathogenic
0.63
CADD
Pathogenic
44
DANN
Uncertain
1.0
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.97
D
Vest4
0.21
GERP RS
4.5

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1057516047; hg19: chr2-47300955; API