9-83969995-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_031263.4(HNRNPK):c.1361+166_1361+167insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 648,324 control chromosomes in the GnomAD database, including 5,413 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1054 hom., cov: 30)
  • Exomes 𝑓: 0.13 (4359 hom.)
• Consequence: HNRNPK NM_031263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.73

Genes affected

HNRNPK (HGNC:5044): (heterogeneous nuclear ribonucleoprotein K) 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 is located in the nucleoplasm and has three repeats of KH domains that binds to RNAs. It is distinct among other hnRNP proteins in its binding preference; it binds tenaciously to poly(C). This protein is also thought to have a role during cell cycle progession. Several alternatively spliced transcript variants have been described for this gene, however, not all of them are fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-83969995-G-GT is Benign according to our data. Variant chr9-83969995-G-GT is described in ClinVar as [Benign]. Clinvar id is 1280999.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPK	NM_031263.4	c.1361+166_1361+167insA		intron_variant		ENST00000376263.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPK	ENST00000376263.8	c.1361+166_1361+167insA		intron_variant		1	NM_031263.4	A1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16099 AN: 152090 Hom.: 1049 Cov.: 30

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.0957

GnomAD4 exome AF: 0.127 AC: 63096 AN: 496116 Hom.: 4359 Cov.: 6 AF XY: 0.126 AC XY: 33622 AN XY: 266640

Gnomad4 AFR exome AF: 0.0352

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.0866

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.106 AC: 16115 AN: 152208 Hom.: 1054 Cov.: 30 AF XY: 0.108 AC XY: 8031 AN XY: 74428

Gnomad4 AFR AF: 0.0348

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0865

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.0947

Alfa AF: 0.0537 Hom.: 66

Bravo AF: 0.0989

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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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: rs3214659; hg19: chr9-86584910;