9-83969995-G-GT

Variant names:

• chr9-83969995-G-GT
• rs3214659
• NM_031263.4:c.1361+166dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_031263.4(HNRNPK):​c.1361+166dupA 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
• 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)

MIR7-1 (HGNC:31638): (microRNA 7-1) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.1361+166dupA		intron	N/A	NP_112553.1	P61978-2
	HNRNPK	NM_002140.5		c.1361+166dupA		intron	N/A	NP_002131.2
	HNRNPK	NM_001318188.2		c.1361+166dupA		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.1361+166dupA		intron	N/A	ENSP00000365439.3	P61978-2
	HNRNPK	ENST00000376281.8	TSL:1	c.1361+166dupA		intron	N/A	ENSP00000365458.4	P61978-2
	HNRNPK	ENST00000360384.9	TSL:1	c.1361+166dupA		intron	N/A	ENSP00000353552.5	P61978-1

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

African (AFR) AF: 0.0352 AC: 464 AN: 13188

American (AMR) AF: 0.121 AC: 2604 AN: 21548

Ashkenazi Jewish (ASJ) AF: 0.0866 AC: 1355 AN: 15654

East Asian (EAS) AF: 0.112 AC: 3461 AN: 30852

South Asian (SAS) AF: 0.104 AC: 5369 AN: 51778

European-Finnish (FIN) AF: 0.155 AC: 5269 AN: 33886

Middle Eastern (MID) AF: 0.0437 AC: 92 AN: 2104

European-Non Finnish (NFE) AF: 0.138 AC: 41196 AN: 299510

Other (OTH) AF: 0.119 AC: 3286 AN: 27596

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

African (AFR) AF: 0.0348 AC: 1445 AN: 41524

American (AMR) AF: 0.126 AC: 1922 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 300 AN: 3470

East Asian (EAS) AF: 0.119 AC: 619 AN: 5190

South Asian (SAS) AF: 0.104 AC: 501 AN: 4822

European-Finnish (FIN) AF: 0.158 AC: 1678 AN: 10590

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9314 AN: 68002

Other (OTH) AF: 0.0947 AC: 200 AN: 2112

Alfa AF: 0.0537 Hom.: 66

Bravo AF: 0.0989

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

ClinVar submissions

Significance: 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		2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3214659; hg19: chr9-86584910;