X-101411965-GCCA-G

Variant names:

• chrX-101411965-GCCA-G
• rs782013153
• ENST00000409170.3:c.334_336delCCA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

The NM_001199973.2(RPL36A-HNRNPH2):​c.334_336delCCA​(p.Pro112del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000401 in 1,148,264 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., 4 hem., cov: 21)
  • Exomes 𝑓: 0.000031 (0 hom. 8 hem.)
• Consequence: RPL36A-HNRNPH2 NM_001199973.2 conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.09

Genes affected

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001199973.2. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant X-101411965-GCCA-G is Benign according to our data. Variant chrX-101411965-GCCA-G is described in ClinVar as [Likely_benign]. Clinvar id is 3778084.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPH2	NM_019597.5	c.-20_-18delCCA		5_prime_UTR_variant	Exon 2 of 2	ENST00000316594.6	NP_062543.1
RPL36A-HNRNPH2	NM_001199973.2	c.334_336delCCA	p.Pro112del	conservative_inframe_deletion	Exon 5 of 5		NP_001186902.2
RPL36A-HNRNPH2	NM_001199974.2	c.211_213delCCA	p.Pro71del	conservative_inframe_deletion	Exon 4 of 4		NP_001186903.2
HNRNPH2	NM_001032393.3	c.-20_-18delCCA		5_prime_UTR_variant	Exon 2 of 2		NP_001027565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL36A-HNRNPH2	ENST00000409170.3	c.334_336delCCA	p.Pro112del	conservative_inframe_deletion	Exon 5 of 5	4		ENSP00000386655.4
HNRNPH2	ENST00000316594	c.-20_-18delCCA		5_prime_UTR_variant	Exon 2 of 2	1	NM_019597.5	ENSP00000361927.2
RPL36A-HNRNPH2	ENST00000409338.5	c.211_213delCCA	p.Pro71del	conservative_inframe_deletion	Exon 4 of 4	4		ENSP00000386974.2

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 13 AN: 103938 Hom.: 0 Cov.: 21 AF XY: 0.000144 AC XY: 4 AN XY: 27830

Gnomad AFR AF: 0.000428

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000487 AC: 7 AN: 143777 Hom.: 0 AF XY: 0.0000437 AC XY: 2 AN XY: 45795

Gnomad AFR exome AF: 0.000491

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000216

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000306 AC: 32 AN: 1044287 Hom.: 0 AF XY: 0.0000240 AC XY: 8 AN XY: 333087

Gnomad4 AFR exome AF: 0.000841

Gnomad4 AMR exome AF: 0.0000410

Gnomad4 ASJ exome AF: 0.000416

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000245

Gnomad4 OTH exome AF: 0.0000460

GnomAD4 genome AF: 0.000135 AC: 14 AN: 103977 Hom.: 0 Cov.: 21 AF XY: 0.000143 AC XY: 4 AN XY: 27881

Gnomad4 AFR AF: 0.000463

Gnomad4 AMR AF: 0.000106

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000212

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RPL36A-HNRNPH2: PM4:Supporting, BS2 -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs782013153; hg19: chrX-100666953;