Variant 16-75647898-G-A 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_018975.4(TERF2IP):c.16G>A(p.Asp6Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,454,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TERF2IP
NM_018975.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.21

Variant links:

Genes affected

TERF2IP (HGNC:19246): (TERF2 interacting protein) Enables G-rich strand telomeric DNA binding activity and phosphatase binding activity. Involved in several processes, including positive regulation of NIK/NF-kappaB signaling; regulation of nucleobase-containing compound metabolic process; and regulation of protein modification process. Located in chromosome, telomeric region; cytosol; and nuclear body. Part of shelterin complex. [provided by Alliance of Genome Resources, Apr 2022]

TERF2IP links:

KARS1 (HGNC:):

KARS1 links:

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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=0.1778459).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERF2IP	NM_018975.4 linkuse as main transcript	c.16G>A	p.Asp6Asn	missense_variant	1/3	ENST00000300086.5	NP_061848.2	Q9NYB0
TERF2IP	XM_047434216.1 linkuse as main transcript	c.16G>A	p.Asp6Asn	missense_variant	1/2		XP_047290172.1
TERF2IP	NR_144545.2 linkuse as main transcript	n.126G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TERF2IP	ENST00000300086.5 linkuse as main transcript	c.16G>A	p.Asp6Asn	missense_variant	1/3	1	NM_018975.4	ENSP00000300086.4	Q9NYB0
KARS1	ENST00000566560.5 linkuse as main transcript	n.176+570C>T		intron_variant		1
TERF2IP	ENST00000653858.1 linkuse as main transcript	c.16G>A	p.Asp6Asn	missense_variant	1/4			ENSP00000499565.1	A0A590UJT3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248982

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134770

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1454696

Hom.:

Cov.:

AF XY:

0.00000692

AC XY:

AN XY:

722358

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 27, 2024

The p.D6N variant (also known as c.16G>A), located in coding exon 1 of the TERF2IP gene, results from a G to A substitution at nucleotide position 16. The aspartic acid at codon 6 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.60

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.060

Eigen_PC

Benign

0.054

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.82

M_CAP

Benign

0.081

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.52

REVEL

Benign

0.15

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.011

Polyphen

0.079

Vest4

0.19

MutPred

0.49

Gain of helix (P = 0.0696);

MVP

0.75

MPC

1.2

ClinPred

0.47

GERP RS

4.8

Varity_R

0.22

gMVP

0.48

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