13-52642885-T-G

Variant names:

• chr13-52642885-T-G
• NM_001389320.1:c.393T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001389320.1(HNRNPA1L2):​c.393T>G​(p.Ile131Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,390 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HNRNPA1L2 NM_001389320.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.80

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPA1L2	NM_001389320.1	c.393T>G	p.Ile131Met	missense_variant	Exon 1 of 1	ENST00000357495.5	NP_001376249.1
HNRNPA1L2	NM_001011724.3	c.393T>G	p.Ile131Met	missense_variant	Exon 7 of 7		NP_001011724.1
HNRNPA1L2	NM_001011725.3	c.393T>G	p.Ile131Met	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.393T>G	p.Ile131Met	missense_variant	Exon 1 of 1	6	NM_001389320.1	ENSP00000350090.2
ENSG00000273784	ENST00000683187.1	n.1270T>G		non_coding_transcript_exon_variant	Exon 6 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444390 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718944

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.393T>G (p.I131M) alteration is located in exon 7 (coding exon 1) of the HNRNPA1L2 gene. This alteration results from a T to G substitution at nucleotide position 393, causing the isoleucine (I) at amino acid position 131 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0061	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	-0.097	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.059	T
Polyphen		0.98	D
Vest4		0.47
MutPred		0.65		Gain of catalytic residue at V133 (P = 8e-04);
MVP		0.53
ClinPred		0.77	D
GERP RS		-0.70
Varity_R		0.15
gMVP		0.32

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: chr13-53217020;