9-83969454-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_031263.4(HNRNPK):c.1362-15del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,548,034 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: HNRNPK NM_031263.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.19

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 9-83969454-GA-G is Benign according to our data. Variant chr9-83969454-GA-G is described in ClinVar as [Benign]. Clinvar id is 1974011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000125 (19/151588) while in subpopulation SAS AF= 0.000208 (1/4806). AF 95% confidence interval is 0.0000792. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPK	NM_031263.4	c.1362-15del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000376263.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPK	ENST00000376263.8	c.1362-15del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_031263.4	A1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 151588 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000287

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000884

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000168 AC: 36 AN: 214284 Hom.: 0 AF XY: 0.000170 AC XY: 20 AN XY: 117952

Gnomad AFR exome AF: 0.000288

Gnomad AMR exome AF: 0.0000387

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000184

Gnomad SAS exome AF: 0.000199

Gnomad FIN exome AF: 0.000336

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.000198

GnomAD4 exome AF: 0.000125 AC: 175 AN: 1396446 Hom.: 1 Cov.: 26 AF XY: 0.000116 AC XY: 81 AN XY: 696980

Gnomad4 AFR exome AF: 0.000131

Gnomad4 AMR exome AF: 0.000111

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000152

Gnomad4 SAS exome AF: 0.000188

Gnomad4 FIN exome AF: 0.000267

Gnomad4 NFE exome AF: 0.000113

Gnomad4 OTH exome AF: 0.000155

GnomAD4 genome AF: 0.000125 AC: 19 AN: 151588 Hom.: 0 Cov.: 33 AF XY: 0.000162 AC XY: 12 AN XY: 73988

Gnomad4 AFR AF: 0.000170

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000287

Gnomad4 NFE AF: 0.0000884

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000982

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

Invitae

Jan 20, 2024

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs749772524; hg19: chr9-86584369;