rs167203

chr9-83978399-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_031263.4(HNRNPK):c.-54C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,425,156 control chromosomes in the GnomAD database, including 33,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3653 hom., cov: 31)
  • Exomes 𝑓: 0.21 (29397 hom.)
• Consequence: HNRNPK NM_031263.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.86

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 9-83978399-G-C is Benign according to our data. Variant chr9-83978399-G-C is described in ClinVar as [Benign]. Clinvar id is 1285706.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPK	NM_031263.4	c.-54C>G		5_prime_UTR_variant	2/17	ENST00000376263.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPK	ENST00000376263.8	c.-54C>G		5_prime_UTR_variant	2/17	1	NM_031263.4	A1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32073 AN: 150334 Hom.: 3656 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.00137

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.208 AC: 265136 AN: 1274756 Hom.: 29397 Cov.: 27 AF XY: 0.208 AC XY: 129726 AN XY: 622706

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.000548

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.213 AC: 32078 AN: 150400 Hom.: 3653 Cov.: 31 AF XY: 0.214 AC XY: 15659 AN XY: 73308

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.00137

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.220

Alfa AF: 0.223 Hom.: 506

Bravo AF: 0.207

Asia WGS AF: 0.0920 AC: 322 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 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	16
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs167203; hg19: chr9-86593314; COSMIC: COSV57935884; COSMIC: COSV57935884;