rs144879228

Variant names:

• chr13-52642538-C-A
• NM_001389320.1:c.46C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-52642538-C-A
• chr13-52642538-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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. 12/21 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.94

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]

ENSG00000273784 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32661894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPA1L2	NM_001389320.1	c.46C>A	p.Leu16Ile	missense_variant	Exon 1 of 1	ENST00000357495.5	NP_001376249.1
HNRNPA1L2	NM_001011724.3	c.46C>A	p.Leu16Ile	missense_variant	Exon 7 of 7		NP_001011724.1
HNRNPA1L2	NM_001011725.3	c.46C>A	p.Leu16Ile	missense_variant	Exon 6 of 6		NP_001011725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPA1L2	ENST00000357495.5	c.46C>A	p.Leu16Ile	missense_variant	Exon 1 of 1	6	NM_001389320.1	ENSP00000350090.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1459702 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 726160

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: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.098
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.32	N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.14
Sift	Benign	0.032	D
Sift4G	Benign	0.078	T
Polyphen		1.0	D
Vest4		0.45
MutPred		0.53		Gain of catalytic residue at L21 (P = 0);
MVP		0.13
ClinPred		0.80	D
GERP RS		0.35
Varity_R		0.064
gMVP		0.33

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.

Other links and lift over

hg19: chr13-53216673;