5-134411725-T-G

Variant names:

• chr5-134411725-T-G
• rs372506709
• NM_080656.3:c.130A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080656.3(CDKN2AIPNL):​c.130A>C​(p.Ile44Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,460,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I44V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: CDKN2AIPNL NM_080656.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.900
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20825106).

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.130A>C	p.Ile44Leu	missense	Exon 1 of 3	NP_542387.1	Q96HQ2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2AIPNL	ENST00000458198.3	TSL:1 MANE Select	c.130A>C	p.Ile44Leu	missense	Exon 1 of 3	ENSP00000394183.2	Q96HQ2-1
	CDKN2AIPNL	ENST00000395009.3	TSL:1	c.130A>C	p.Ile44Leu	missense	Exon 1 of 2	ENSP00000378456.3	Q96HQ2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247436 AF XY: 0.00000743

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000896

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1460924 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 726756

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5558

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111852

Other (OTH) AF: 0.0000166 AC: 1 AN: 60322

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.85	L
PhyloP100		0.90
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.072
Sift	Benign	0.47	T
Sift4G	Benign	0.30	T
Polyphen		0.0090	B
Vest4		0.39
MutPred		0.47		Gain of disorder (P = 0.039)
MVP		0.32
MPC		0.40
ClinPred		0.31	T
GERP RS		4.5
PromoterAI		-0.012	Neutral
Varity_R		0.45
gMVP		0.72
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs372506709; hg19: chr5-133747416;