Variant 4-183445609-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_017632.4(CDKN2AIP):c.347C>T(p.Thr116Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000762 in 1,457,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

CDKN2AIP
NM_017632.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

Variant links:

Genes affected

CDKN2AIP (HGNC:24325): (CDKN2A interacting protein) The protein encoded by this gene regulates the DNA damage response through several different signaling pathways. One such pathway is the p53-HDM2-p21(WAF1) pathway, which is critical to the DNA damage response. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

CDKN2AIP links:

CDKN2AIP (HGNC:):

CDKN2AIP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.105896145).

BS2

High AC in GnomAdExome4 at 111 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN2AIP	NM_017632.4 linkuse as main transcript	c.347C>T	p.Thr116Ile	missense_variant	2/3	ENST00000504169.2	NP_060102.1	Q9NXV6
CDKN2AIP	NM_001317343.2 linkuse as main transcript	c.347C>T	p.Thr116Ile	missense_variant	2/3		NP_001304272.1	Q9NXV6J3KNE1B3KTW3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDKN2AIP	ENST00000504169.2 linkuse as main transcript	c.347C>T	p.Thr116Ile	missense_variant	2/3	1	NM_017632.4	ENSP00000427108.1	Q9NXV6
CDKN2AIP	ENST00000510928.1 linkuse as main transcript	c.347C>T	p.Thr116Ile	missense_variant	2/2	2		ENSP00000421308.1	D6RGD2
CDKN2AIP	ENST00000302350.4 linkuse as main transcript	c.347C>T	p.Thr116Ile	missense_variant	2/3	2		ENSP00000303788.4	J3KNE1
CDKN2AIP	ENST00000506835.1 linkuse as main transcript	n.191C>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251470

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000762

AC:

111

AN:

1457432

Hom.:

Cov.:

AF XY:

0.0000662

AC XY:

AN XY:

725434

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.0000966

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Oct 27, 2022

The c.347C>T (p.T116I) alteration is located in exon 2 (coding exon 2) of the CDKN2AIP gene. This alteration results from a C to T substitution at nucleotide position 347, causing the threonine (T) at amino acid position 116 to be replaced by an isoleucine (I). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;T

Eigen

Benign

-0.079

Eigen_PC

Benign

0.059

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.4

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.053

Sift

Benign

0.058

T;T;T

Sift4G

Benign

0.077

T;T;T

Polyphen

0.029

B;.;.

Vest4

0.33

MutPred

0.45

Gain of glycosylation at Y115 (P = 0.0098);Gain of glycosylation at Y115 (P = 0.0098);Gain of glycosylation at Y115 (P = 0.0098);

MVP

0.17

MPC

0.063

ClinPred

0.29

GERP RS

4.4

Varity_R

0.18

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