Genetic Variant NM_080656.3:c.28G>A (chr5-134411827-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 13/21 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

Publications

0 publications found

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:

ENSG00000299601 (HGNC:):

ENSG00000299601 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080656.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2AIPNL	NM_080656.3	MANE Select	c.28G>A	p.Val10Met	missense	Exon 1 of 3	NP_542387.1	Q96HQ2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDKN2AIPNL	ENST00000458198.3	TSL:1 MANE Select	c.28G>A	p.Val10Met	missense	Exon 1 of 3	ENSP00000394183.2	Q96HQ2-1
CDKN2AIPNL	ENST00000395009.3	TSL:1	c.28G>A	p.Val10Met	missense	Exon 1 of 2	ENSP00000378456.3	Q96HQ2-2
ENSG00000299601	ENST00000764987.1		n.-181C>T		upstream_gene	N/A

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

GnomAD2 exomes

AF:

0.0000904

AC:

AN:

188084

AF XY:

0.0000965

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 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

African (AFR)

AF:

0.00

AC:

AN:

32210

American (AMR)

AF:

0.0000247

AC:

AN:

40406

Ashkenazi Jewish (ASJ)

AF:

0.000589

AC:

AN:

25452

East Asian (EAS)

AF:

0.00

AC:

AN:

37270

South Asian (SAS)

AF:

0.0000242

AC:

AN:

82752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49424

Middle Eastern (MID)

AF:

0.000733

AC:

AN:

5454

European-Non Finnish (NFE)

AF:

0.0000365

AC:

AN:

1096646

Other (OTH)

AF:

0.000102

AC:

AN:

58954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41468

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.036

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.021

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.4

PhyloP100

3.9

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.3

REVEL

Benign

0.21

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Polyphen

0.010

Vest4

0.25

MVP

0.29

MPC

0.40

ClinPred

0.17

GERP RS

2.8

PromoterAI

0.44

Neutral

(source)

Varity_R

0.19

gMVP

0.77

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over