rs3027580

Variant names:

• chrX-101408672-C-G
• rs3027580
• NM_019597.5:c.-54+353C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019597.5(HNRNPH2):​c.-54+353C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 111,268 control chromosomes in the GnomAD database, including 205 homozygotes. There are 2,427 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.069 (205 hom., 2427 hem., cov: 22)
• Consequence: HNRNPH2 NM_019597.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.432
• Publications: 2 publications found

Genes affected

HNRNPH2 (HGNC:5042): (heterogeneous nuclear ribonucleoprotein H2) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has three repeats of quasi-RRM domains that binds to RNAs. It is very similar to the family member HNRPH1. This gene is thought to be involved in Fabray disease and X-linked agammaglobulinemia phenotype. Alternative splicing results in multiple transcript variants encoding the same protein. Read-through transcription between this locus and the ribosomal protein L36a gene has been observed. [provided by RefSeq, Jan 2011]

RPL36A-HNRNPH2 (HGNC:48349): (RPL36A-HNRNPH2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring ribosomal protein L36a and heterogeneous nuclear ribonucleoprotein H2 (H') genes on chromosome X. The read-through transcript produces a protein with similarity to the protein encoded by the upstream locus, ribosomal protein L36a. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant X-101408672-C-G is Benign according to our data. Variant chrX-101408672-C-G is described in ClinVar as Benign. ClinVar VariationId is 1167953.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPH2	NM_019597.5	c.-54+353C>G		intron_variant	Intron 1 of 1	ENST00000316594.6	NP_062543.1
HNRNPH2	NM_001032393.3	c.-54+365C>G		intron_variant	Intron 1 of 1		NP_001027565.1
RPL36A-HNRNPH2	NM_001199973.2	c.301-3264C>G		intron_variant	Intron 4 of 4		NP_001186902.2
RPL36A-HNRNPH2	NM_001199974.2	c.178-3264C>G		intron_variant	Intron 3 of 3		NP_001186903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPH2	ENST00000316594.6	c.-54+353C>G		intron_variant	Intron 1 of 1	1	NM_019597.5	ENSP00000361927.2
RPL36A-HNRNPH2	ENST00000409170.3	c.301-3264C>G		intron_variant	Intron 4 of 4	4		ENSP00000386655.4
RPL36A-HNRNPH2	ENST00000409338.5	c.178-3264C>G		intron_variant	Intron 3 of 3	4		ENSP00000386974.2

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 7660 AN: 111216 Hom.: 206 Cov.: 22

Gnomad AFR AF: 0.0667

Gnomad AMI AF: 0.0988

Gnomad AMR AF: 0.0731

Gnomad ASJ AF: 0.0541

Gnomad EAS AF: 0.0800

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.0420

Gnomad NFE AF: 0.0593

Gnomad OTH AF: 0.0656

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0688 AC: 7654 AN: 111268 Hom.: 205 Cov.: 22 AF XY: 0.0725 AC XY: 2427 AN XY: 33490

African (AFR) AF: 0.0667 AC: 2039 AN: 30581

American (AMR) AF: 0.0731 AC: 771 AN: 10544

Ashkenazi Jewish (ASJ) AF: 0.0541 AC: 143 AN: 2642

East Asian (EAS) AF: 0.0800 AC: 281 AN: 3514

South Asian (SAS) AF: 0.275 AC: 723 AN: 2625

European-Finnish (FIN) AF: 0.0637 AC: 381 AN: 5984

Middle Eastern (MID) AF: 0.0415 AC: 9 AN: 217

European-Non Finnish (NFE) AF: 0.0593 AC: 3140 AN: 52969

Other (OTH) AF: 0.0661 AC: 100 AN: 1514

Alfa AF: 0.0675 Hom.: 360

Bravo AF: 0.0691

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Fabry disease Benign:2

Oct 16, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.64
PhyloP100		0.43
PromoterAI		0.0092	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs3027580; hg19: chrX-100663660;