chr9-83969444-T-TAA

Variant names:

• chr9-83969444-T-TAA
• rs1956719491
• NM_031263.4:c.1362-6_1362-5dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_031263.4(HNRNPK):​c.1362-6_1362-5dupTT variant causes a splice region, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HNRNPK NM_031263.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.78
• Publications: 0 publications found

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]

HNRNPK-AS1 (HGNC:56061): (HNRNPK antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 9-83969444-T-TAA is Benign according to our data. Variant chr9-83969444-T-TAA is described in ClinVar as Likely_benign. ClinVar VariationId is 2133113.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031263.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPK	NM_031263.4	MANE Select	c.1362-6_1362-5dupTT		splice_region intron	N/A	NP_112553.1	P61978-2
	HNRNPK	NM_002140.5		c.1362-6_1362-5dupTT		splice_region intron	N/A	NP_002131.2
	HNRNPK	NM_001318188.2		c.1362-66_1362-65dupTT		intron	N/A	NP_001305117.1	P61978-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPK	ENST00000376263.8	TSL:1 MANE Select	c.1362-6_1362-5dupTT		splice_region intron	N/A	ENSP00000365439.3	P61978-2
	HNRNPK	ENST00000376281.8	TSL:1	c.1362-6_1362-5dupTT		splice_region intron	N/A	ENSP00000365458.4	P61978-2
	HNRNPK	ENST00000360384.9	TSL:1	c.1362-66_1362-65dupTT		intron	N/A	ENSP00000353552.5	P61978-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1956719491; hg19: chr9-86584359;