Variant 1-117075402-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003594.4(TTF2):c.818G>C(p.Ser273Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00396 in 1,614,174 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 92 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 75 hom. )

Consequence

TTF2
NM_003594.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.18

Variant links:

Genes affected

TTF2 (HGNC:12398): (transcription termination factor 2) This gene encodes a member of the SWI2/SNF2 family of proteins, which play a critical role in altering protein-DNA interactions. The encoded protein has been shown to have dsDNA-dependent ATPase activity and RNA polymerase II termination activity. This protein interacts with cell division cycle 5-like, associates with human splicing complexes, and plays a role in pre-mRNA splicing. [provided by RefSeq, Jul 2008]

TTF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002588272).

BP6

Variant 1-117075402-G-C is Benign according to our data. Variant chr1-117075402-G-C is described in ClinVar as [Benign]. Clinvar id is 767690.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTF2	NM_003594.4 linkuse as main transcript	c.818G>C	p.Ser273Thr	missense_variant	5/23	ENST00000369466.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTF2	ENST00000369466.9 linkuse as main transcript	c.818G>C	p.Ser273Thr	missense_variant	5/23	1	NM_003594.4	P1	Q9UNY4-1
TTF2	ENST00000469638.1 linkuse as main transcript	n.108G>C		non_coding_transcript_exon_variant	1/2	2
TTF2	ENST00000470935.1 linkuse as main transcript	n.807G>C		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2868

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0630

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.00541

AC:

1359

AN:

251276

Hom.:

AF XY:

0.00421

AC XY:

572

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.0686

Gnomad AMR exome

AF:

0.00373

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000704

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00240

AC:

3512

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

1580

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0674

Gnomad4 AMR exome

AF:

0.00396

Gnomad4 ASJ exome

AF:

0.00157

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000591

Gnomad4 OTH exome

AF:

0.00498

GnomAD4 genome

AF:

0.0189

AC:

2884

AN:

152282

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1369

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0632

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.00222

Hom.:

Bravo

AF:

0.0212

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0595

AC:

262

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00652

AC:

792

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.040

DANN

Benign

0.76

DEOGEN2

Benign

0.014

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.43

REVEL

Benign

0.12

Sift

Benign

0.29

Sift4G

Benign

0.47

Polyphen

0.0020

Vest4

0.065

MVP

0.65

MPC

0.17

ClinPred

0.0036

GERP RS

-1.2

Varity_R

0.028

gMVP

0.15

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