chr13-52642601-T-G

Variant names:

• chr13-52642601-T-G
• rs1471629072
• NM_001389320.1:c.109T>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001389320.1(HNRNPA1L2):​c.109T>G​(p.Trp37Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. W37R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HNRNPA1L2 NM_001389320.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.75

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPA1L2	NM_001389320.1	MANE Select	c.109T>G	p.Trp37Gly	missense	Exon 1 of 1	NP_001376249.1	Q32P51
	HNRNPA1L2	NM_001011724.3		c.109T>G	p.Trp37Gly	missense	Exon 7 of 7	NP_001011724.1	Q32P51
	HNRNPA1L2	NM_001011725.3		c.109T>G	p.Trp37Gly	missense	Exon 6 of 6	NP_001011725.1	Q32P51

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPA1L2	ENST00000357495.5	TSL:6 MANE Select	c.109T>G	p.Trp37Gly	missense	Exon 1 of 1	ENSP00000350090.2	Q32P51
	ENSG00000273784	ENST00000683187.1		n.986T>G		non_coding_transcript_exon	Exon 6 of 6
	ENSG00000273784	ENST00000740503.1		n.514+5155T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0016	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.30	N
PhyloP100		4.0
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-11	D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.016	D
Polyphen		0.95	P
Vest4		0.58
MutPred		0.71		Gain of disorder (P = 0.0027)
MVP		0.28
ClinPred		0.98	D
GERP RS		-0.70
PromoterAI		0.016	Neutral
Varity_R		0.80
gMVP		0.43
Mutation Taster		=77/23	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: rs1471629072; hg19: chr13-53216736;