dbSNP rs144879228: HNRNPA1L2:p.Leu16Ile (chr13-52642538-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001389320.1(HNRNPA1L2):c.46C>A(p.Leu16Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,459,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L16F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

HNRNPA1L2
NM_001389320.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.94

Publications

0 publications found

Variant links:

Genes affected

HNRNPA1L2 (HGNC:27067): (heterogeneous nuclear ribonucleoprotein A1 like 2) Predicted to enable RNA binding activity. Predicted to be involved in RNA splicing; mRNA processing; and mRNA transport. Predicted to be located in cytoplasm. Predicted to be part of spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

HNRNPA1L2 links:

ENSG00000273784 (HGNC:):

ENSG00000273784 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32661894).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001389320.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HNRNPA1L2	NM_001389320.1	MANE Select	c.46C>A	p.Leu16Ile	missense	Exon 1 of 1	NP_001376249.1	Q32P51
HNRNPA1L2	NM_001011724.3		c.46C>A	p.Leu16Ile	missense	Exon 7 of 7	NP_001011724.1	Q32P51
HNRNPA1L2	NM_001011725.3		c.46C>A	p.Leu16Ile	missense	Exon 6 of 6	NP_001011725.1	Q32P51

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HNRNPA1L2	ENST00000357495.5	TSL:6 MANE Select	c.46C>A	p.Leu16Ile	missense	Exon 1 of 1	ENSP00000350090.2	Q32P51
ENSG00000273784	ENST00000614537.4	TSL:3	n.672C>A		non_coding_transcript_exon	Exon 5 of 5
ENSG00000273784	ENST00000683187.1		n.923C>A		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1459702

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726160

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111826

Other (OTH)

AF:

0.00

AC:

AN:

60206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0079

Eigen

Benign

-0.098

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.67

M_CAP

Benign

0.0024

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.32

PhyloP100

3.9

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.6

REVEL

Benign

0.14

Sift

Benign

0.032

Sift4G

Benign

0.078

Polyphen

1.0

Vest4

0.45

MutPred

0.53

Gain of catalytic residue at L21 (P = 0)

MVP

0.13

ClinPred

0.80

GERP RS

0.35

PromoterAI

0.016

Neutral

(source)

Varity_R

0.064

gMVP

0.33

Mutation Taster

=87/13

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over