NM_001257293.2:c.1118-24dupT

Variant names:

• chr5-179616981-C-CA
• rs34734159
• NM_001257293.2:c.1118-24dupT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001257293.2(HNRNPH1):​c.1118-24dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000897 in 1,114,964 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: HNRNPH1 NM_001257293.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21
• Publications: 0 publications found

Genes affected

HNRNPH1 (HGNC:5041): (heterogeneous nuclear ribonucleoprotein H1) This gene encodes a member of a subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins that complex with heterogeneous nuclear RNA. 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 may 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 bind to RNA and is very similar to the family member HNRPF. This gene may be associated with hereditary lymphedema type I. Alternatively spliced transcript variants have been described [provided by RefSeq, Mar 2012]

HNRNPH1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: G2P
• neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

LOC128966623 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257293.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPH1	NM_001257293.2	MANE Select	c.1118-24dupT		intron	N/A	NP_001244222.1
	HNRNPH1	NM_001364225.2		c.1118-24dupT		intron	N/A	NP_001351154.1
	HNRNPH1	NM_001364226.2		c.1118-24dupT		intron	N/A	NP_001351155.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPH1	ENST00000393432.9	TSL:1 MANE Select	c.1118-24dupT		intron	N/A	ENSP00000377082.4
	HNRNPH1	ENST00000442819.6	TSL:1	c.1118-24dupT		intron	N/A	ENSP00000397797.2
	HNRNPH1	ENST00000502632.5	TSL:2	n.1183dupT		non_coding_transcript_exon	Exon 4 of 7

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 8.97e-7 AC: 1 AN: 1114964 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 565632

African (AFR) AF: 0.00 AC: 0 AN: 29062

American (AMR) AF: 0.00 AC: 0 AN: 42468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23870

East Asian (EAS) AF: 0.00 AC: 0 AN: 39038

South Asian (SAS) AF: 0.00 AC: 0 AN: 80032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5258

European-Non Finnish (NFE) AF: 0.00000126 AC: 1 AN: 793554

Other (OTH) AF: 0.00 AC: 0 AN: 50104

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs34734159; hg19: chr5-179043982;