rs1162759

chr10-68340394-G-Achr10-68340394-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012207.3(HNRNPH3):c.640-780G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 152,266 control chromosomes in the GnomAD database, including 66,877 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.94 (66877 hom., cov: 32)
• Consequence: HNRNPH3 NM_012207.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

Genes affected

HNRNPH3 (HGNC:5043): (heterogeneous nuclear ribonucleoprotein H3) 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 two repeats of quasi-RRM domains that bind to RNAs. It is localized in nuclear bodies of the nucleus. This protein is involved in the splicing process and it also participates in early heat shock-induced splicing arrest by transiently leaving the hnRNP complexes. Several alternatively spliced transcript variants have been noted for this gene, however, not all are fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPH3	NM_012207.3	c.640-780G>A		intron_variant		ENST00000265866.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPH3	ENST00000265866.12	c.640-780G>A		intron_variant		1	NM_012207.3	P3

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142475 AN: 152148 Hom.: 66833 Cov.: 32

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.990

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.952

Gnomad OTH AF: 0.949

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

GnomAD4 genome AF: 0.936 AC: 142576 AN: 152266 Hom.: 66877 Cov.: 32 AF XY: 0.938 AC XY: 69867 AN XY: 74460

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.962

Gnomad4 ASJ AF: 0.963

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.991

Gnomad4 FIN AF: 0.954

Gnomad4 NFE AF: 0.952

Gnomad4 OTH AF: 0.949

Alfa AF: 0.938 Hom.: 15278

Bravo AF: 0.932

Asia WGS AF: 0.985 AC: 3427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	1.6
Dann	Benign	0.83

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: rs1162759; hg19: chr10-70100151;