14-90646962-T-C

Variant summary

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

The NM_001010854.2(TTC7B):ā€‹c.1579A>Gā€‹(p.Ile527Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

TTC7B
NM_001010854.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.57
Variant links:
Genes affected
TTC7B (HGNC:19858): (tetratricopeptide repeat domain 7B) Involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
TTC7B-AS1 (HGNC:56196): (TTC7B antisense RNA 1)

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=0.12233123).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TTC7BNM_001010854.2 linkuse as main transcriptc.1579A>G p.Ile527Val missense_variant 14/20 ENST00000328459.11
TTC7B-AS1NR_110134.1 linkuse as main transcriptn.549T>C non_coding_transcript_exon_variant 3/5
TTC7BNM_001401365.1 linkuse as main transcriptc.1579A>G p.Ile527Val missense_variant 14/22
TTC7BNM_001320421.2 linkuse as main transcriptc.1273A>G p.Ile425Val missense_variant 14/21

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TTC7BENST00000328459.11 linkuse as main transcriptc.1579A>G p.Ile527Val missense_variant 14/201 NM_001010854.2 P1Q86TV6-1
TTC7B-AS1ENST00000557007.1 linkuse as main transcriptn.538T>C non_coding_transcript_exon_variant 3/51

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152184
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251438
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461812
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152184
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 14, 2022The c.1579A>G (p.I527V) alteration is located in exon 14 (coding exon 14) of the TTC7B gene. This alteration results from a A to G substitution at nucleotide position 1579, causing the isoleucine (I) at amino acid position 527 to be replaced by a valine (V). 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
0.071
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
20
DANN
Benign
0.96
DEOGEN2
Benign
0.28
T
Eigen
Benign
-0.17
Eigen_PC
Benign
0.074
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
0.20
N
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.51
N
REVEL
Benign
0.23
Sift
Benign
0.075
T
Sift4G
Benign
0.18
T
Polyphen
0.0020
B
Vest4
0.12
MVP
0.31
MPC
0.30
ClinPred
0.14
T
GERP RS
5.8
Varity_R
0.14
gMVP
0.070

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: rs375472472; hg19: chr14-91113306; API