Variant 4-183445035-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017632.4(CDKN2AIP):c.238A>G(p.Met80Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,449,536 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CDKN2AIP
NM_017632.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.23

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN2AIP	NM_017632.4 linkuse as main transcript	c.238A>G	p.Met80Val	missense_variant	1/3	ENST00000504169.2	NP_060102.1	Q9NXV6
CDKN2AIP	NM_001317343.2 linkuse as main transcript	c.238A>G	p.Met80Val	missense_variant	1/3		NP_001304272.1	Q9NXV6J3KNE1B3KTW3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDKN2AIP	ENST00000504169.2 linkuse as main transcript	c.238A>G	p.Met80Val	missense_variant	1/3	1	NM_017632.4	ENSP00000427108.1	Q9NXV6
CDKN2AIP	ENST00000510928.1 linkuse as main transcript	c.238A>G	p.Met80Val	missense_variant	1/2	2		ENSP00000421308.1	D6RGD2
CDKN2AIP	ENST00000302350.4 linkuse as main transcript	c.238A>G	p.Met80Val	missense_variant	1/3	2		ENSP00000303788.4	J3KNE1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1449536

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718568

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 29, 2024

The c.238A>G (p.M80V) alteration is located in exon 1 (coding exon 1) of the CDKN2AIP gene. This alteration results from a A to G substitution at nucleotide position 238, causing the methionine (M) at amino acid position 80 to be replaced by a valine (V). 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

Benign

0.22

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;T;T

Eigen

Benign

0.067

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.1

M;.;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.4

N;D;D

REVEL

Benign

0.25

Sift

Benign

0.072

T;T;T

Sift4G

Benign

0.21

T;D;D

Polyphen

0.49

P;.;.

Vest4

0.64

MutPred

0.66

Gain of catalytic residue at M80 (P = 0.0941);Gain of catalytic residue at M80 (P = 0.0941);Gain of catalytic residue at M80 (P = 0.0941);

MVP

0.78

MPC

1.1

ClinPred

0.91

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.51

gMVP

0.56

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over