2-47060786-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020458.4(TTC7A):ā€‹c.2170C>Gā€‹(p.Gln724Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. Q724K) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

TTC7A
NM_020458.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16251165).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TTC7ANM_020458.4 linkuse as main transcriptc.2170C>G p.Gln724Glu missense_variant 19/20 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.2170C>G p.Gln724Glu missense_variant 19/202 NM_020458.4 ENSP00000316699.5 Q9ULT0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249682
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134822
show subpopulations
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:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457630
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
724428
show subpopulations
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
19
DANN
Benign
0.96
DEOGEN2
Benign
0.067
.;T;.
Eigen
Benign
-0.074
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.93
D;D;D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
1.4
.;L;.
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.1
N;N;N
REVEL
Benign
0.14
Sift
Benign
0.66
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0040
B;B;.
Vest4
0.49
MutPred
0.34
.;.;Gain of ubiquitination at K752 (P = 0.0685);
MVP
0.80
MPC
0.078
ClinPred
0.12
T
GERP RS
5.8
Varity_R
0.098
gMVP
0.34

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

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

Other links and lift over

dbSNP: rs140166160; hg19: chr2-47287925; API