Variant 14-90644085-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001010854.2(TTC7B):c.1714A>G(p.Ile572Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TTC7B
NM_001010854.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85

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 links:

TTC7B-AS1 (HGNC:56196): (TTC7B antisense RNA 1)

TTC7B-AS1 links:

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=0.15535039).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TTC7B	NM_001010854.2 linkuse as main transcript	c.1714A>G	p.Ile572Val	missense_variant	15/20	ENST00000328459.11
TTC7B-AS1	NR_110134.1 linkuse as main transcript	n.103-659T>C		intron_variant, non_coding_transcript_variant
TTC7B	NM_001401365.1 linkuse as main transcript	c.1714A>G	p.Ile572Val	missense_variant	15/22
TTC7B	NM_001320421.2 linkuse as main transcript	c.1408A>G	p.Ile470Val	missense_variant	15/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC7B	ENST00000328459.11 linkuse as main transcript	c.1714A>G	p.Ile572Val	missense_variant	15/20	1	NM_001010854.2	P1	Q86TV6-1
TTC7B-AS1	ENST00000557007.1 linkuse as main transcript	n.92-659T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152022

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

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

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 submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.1714A>G (p.I572V) alteration is located in exon 15 (coding exon 15) of the TTC7B gene. This alteration results from a A to G substitution at nucleotide position 1714, causing the isoleucine (I) at amino acid position 572 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

0.070

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

Cadd

Benign

Dann

Benign

0.75

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

T;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.96

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.10

Sift

Benign

0.29

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.0020

B;.

Vest4

0.29

MutPred

0.55

Gain of catalytic residue at D573 (P = 2e-04);.;

MVP

0.42

MPC

0.30

ClinPred

0.38

GERP RS

3.5

Varity_R

0.068

gMVP

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over