Variant 14-90578192-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001010854.2(TTC7B):c.2224C>A(p.Leu742Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00644 in 1,614,154 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0067 ( 35 hom. )

Consequence

TTC7B
NM_001010854.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.10

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009799242).

BP6

Variant 14-90578192-G-T is Benign according to our data. Variant chr14-90578192-G-T is described in ClinVar as [Benign]. Clinvar id is 773559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TTC7B	NM_001010854.2 linkuse as main transcript	c.2224C>A	p.Leu742Ile	missense_variant	19/20	ENST00000328459.11
TTC7B	NM_001401365.1 linkuse as main transcript	c.2437C>A	p.Leu813Ile	missense_variant	21/22
TTC7B	NM_001320421.2 linkuse as main transcript	c.1969C>A	p.Leu657Ile	missense_variant	20/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC7B	ENST00000328459.11 linkuse as main transcript	c.2224C>A	p.Leu742Ile	missense_variant	19/20	1	NM_001010854.2	P1	Q86TV6-1

Frequencies

GnomAD3 genomes

AF:

0.00426

AC:

649

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00747

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00405

AC:

1015

AN:

250748

Hom.:

AF XY:

0.00405

AC XY:

549

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00232

Gnomad FIN exome

AF:

0.00222

Gnomad NFE exome

AF:

0.00716

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00667

AC:

9750

AN:

1461772

Hom.:

Cov.:

AF XY:

0.00638

AC XY:

4641

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00208

Gnomad4 FIN exome

AF:

0.00198

Gnomad4 NFE exome

AF:

0.00819

Gnomad4 OTH exome

AF:

0.00439

GnomAD4 genome

AF:

0.00426

AC:

649

AN:

152382

Hom.:

Cov.:

AF XY:

0.00401

AC XY:

299

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.00747

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00642

Hom.:

Bravo

AF:

0.00436

TwinsUK

AF:

0.0140

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00756

AC:

ExAC

AF:

0.00400

AC:

485

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00540

EpiControl

AF:

0.00617

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.32

T;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.0098

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.34

N;N

REVEL

Benign

0.21

Sift

Benign

0.31

T;T

Sift4G

Benign

0.39

T;T

Polyphen

1.0

D;.

Vest4

0.49

MVP

0.15

MPC

1.0

ClinPred

0.051

GERP RS

5.3

Varity_R

0.25

gMVP

0.12

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