Genetic Variant CDKN2AIPNL:p.Val10Met (chr5-134411827-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080656.3(CDKN2AIPNL):c.28G>A(p.Val10Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000512 in 1,580,788 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 1 hom. )

Consequence

CDKN2AIPNL
NM_080656.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

Variant links:

Genes affected

CDKN2AIPNL (HGNC:30545): (CDKN2A interacting protein N-terminal like) Predicted to be active in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CDKN2AIPNL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039554954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2AIPNL	NM_080656.3 link	c.28G>A	p.Val10Met	missense_variant	Exon 1 of 3	ENST00000458198.3	NP_542387.1	Q96HQ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2AIPNL	ENST00000458198.3 link	c.28G>A	p.Val10Met	missense_variant	Exon 1 of 3	1	NM_080656.3	ENSP00000394183.2		Q96HQ2-1
CDKN2AIPNL	ENST00000395009.3 link	c.28G>A	p.Val10Met	missense_variant	Exon 1 of 2	1		ENSP00000378456.3		Q96HQ2-2

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000904

AC:

AN:

188084

Hom.:

AF XY:

0.0000965

AC XY:

AN XY:

103584

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000918

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000893

Gnomad OTH exome

AF:

0.000409

GnomAD4 exome

AF:

0.0000476

AC:

AN:

1428568

Hom.:

Cov.:

AF XY:

0.0000466

AC XY:

AN XY:

708384

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000247

Gnomad4 ASJ exome

AF:

0.000589

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000242

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000365

Gnomad4 OTH exome

AF:

0.000102

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000133

AC:

ExAC

AF:

0.000104

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.28G>A (p.V10M) alteration is located in exon 1 (coding exon 1) of the CDKN2AIPNL gene. This alteration results from a G to A substitution at nucleotide position 28, causing the valine (V) at amino acid position 10 to be replaced by a methionine (M). 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

0.27

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.036

T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.040

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.21

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.010

B;B

Vest4

0.25

MVP

0.29

MPC

0.40

ClinPred

0.17

GERP RS

2.8

Varity_R

0.19

gMVP

0.77

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