14-24240145-C-T

Position:

chr14-24240145-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001099274.3(TINF2):c.1140G>A(p.Pro380Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,613,890 control chromosomes in the GnomAD database, including 1,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 863 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 780 hom. )

Consequence

TINF2
NM_001099274.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.183

Variant links:

Genes affected

TINF2 (HGNC:11824): (TERF1 interacting nuclear factor 2) This gene encodes one of the proteins of the shelterin, or telosome, complex which protects telomeres by allowing the cell to distinguish between telomeres and regions of DNA damage. The protein encoded by this gene is a critical part of shelterin; it interacts with the three DNA-binding proteins of the shelterin complex, and it is important for assembly of the complex. Mutations in this gene cause dyskeratosis congenita (DKC), an inherited bone marrow failure syndrome. [provided by RefSeq, Mar 2010]

TINF2 links:

TINF2 (HGNC:):

TINF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 14-24240145-C-T is Benign according to our data. Variant chr14-24240145-C-T is described in ClinVar as [Benign]. Clinvar id is 312946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.183 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TINF2	NM_001099274.3 linkuse as main transcript	c.1140G>A	p.Pro380Pro	synonymous_variant	8/9	ENST00000267415.12	NP_001092744.1	Q9BSI4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TINF2	ENST00000267415.12 linkuse as main transcript	c.1140G>A	p.Pro380Pro	synonymous_variant	8/9	1	NM_001099274.3	ENSP00000267415.7		Q9BSI4-1

Frequencies

GnomAD3 genomes

AF:

0.0589

AC:

8944

AN:

151886

Hom.:

858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0268

Gnomad ASJ

AF:

0.000867

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.0459

GnomAD3 exomes

AF:

0.0150

AC:

3737

AN:

249562

Hom.:

340

AF XY:

0.0112

AC XY:

1523

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000856

Gnomad OTH exome

AF:

0.00874

GnomAD4 exome

AF:

0.00621

AC:

9076

AN:

1461886

Hom.:

780

Cov.:

AF XY:

0.00535

AC XY:

3894

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.208

Gnomad4 AMR exome

AF:

0.0128

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000460

Gnomad4 OTH exome

AF:

0.0144

GnomAD4 genome

AF:

0.0590

AC:

8970

AN:

152004

Hom.:

863

Cov.:

AF XY:

0.0576

AC XY:

4277

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.0268

Gnomad4 ASJ

AF:

0.000867

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.00112

Gnomad4 OTH

AF:

0.0454

Alfa

AF:

0.0329

Hom.:

255

Bravo

AF:

0.0668

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 14, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Apr 04, 2017

- -

Dyskeratosis congenita, autosomal dominant 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Revesz syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Dyskeratosis congenita

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.6

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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