9-83969988-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_031263.4(HNRNPK):c.1361+174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 646,340 control chromosomes in the GnomAD database, including 151,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (41476 hom., cov: 33)
  • Exomes 𝑓: 0.66 (110258 hom.)
• Consequence: HNRNPK NM_031263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.709

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 9-83969988-A-G is Benign according to our data. Variant chr9-83969988-A-G is described in ClinVar as [Benign]. Clinvar id is 1222255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPK	NM_031263.4	c.1361+174T>C		intron_variant		ENST00000376263.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPK	ENST00000376263.8	c.1361+174T>C		intron_variant		1	NM_031263.4	A1

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110188 AN: 152050 Hom.: 41406 Cov.: 33

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.691

GnomAD4 exome AF: 0.663 AC: 327795 AN: 494172 Hom.: 110258 Cov.: 5 AF XY: 0.662 AC XY: 176344 AN XY: 266338

Gnomad4 AFR exome AF: 0.931

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.691

Gnomad4 EAS exome AF: 0.522

Gnomad4 SAS exome AF: 0.657

Gnomad4 FIN exome AF: 0.716

Gnomad4 NFE exome AF: 0.671

Gnomad4 OTH exome AF: 0.678

GnomAD4 genome AF: 0.725 AC: 110313 AN: 152168 Hom.: 41476 Cov.: 33 AF XY: 0.722 AC XY: 53749 AN XY: 74402

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.693

Alfa AF: 0.682 Hom.: 16056

Bravo AF: 0.721

Asia WGS AF: 0.609 AC: 2116 AN: 3476

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 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	2.4
Dann	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs296885; hg19: chr9-86584903;