chr9-83980155-C-T

Variant names:

• chr9-83980155-C-T
• rs296887
• NM_031263.4:c.-110G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_031263.4(HNRNPK):​c.-110G>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,386 control chromosomes in the GnomAD database, including 7,561 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (7550 hom., cov: 33)
  • Exomes 𝑓: 0.30 (11 hom.)
• Consequence: HNRNPK NM_031263.4 splice_region
• Scores: Splicing: ADA: 0.0001644
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 20 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]

RMI1 (HGNC:25764): (RecQ mediated genome instability 1) Predicted to enable nucleotide binding activity. Predicted to be involved in double-strand break repair via homologous recombination and resolution of meiotic recombination intermediates. Predicted to act upstream of or within glucose homeostasis; reduction of food intake in response to dietary excess; and response to glucose. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000309273 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 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.-110G>A		splice_region	Exon 1 of 17	NP_112553.1	P61978-2
	HNRNPK	NM_031263.4	MANE Select	c.-110G>A		5_prime_UTR	Exon 1 of 17	NP_112553.1	P61978-2
	HNRNPK	NM_001318188.2		c.-110G>A		splice_region	Exon 1 of 17	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.-110G>A		splice_region	Exon 1 of 17	ENSP00000365439.3	P61978-2
	HNRNPK	ENST00000360384.9	TSL:1	c.-110G>A		splice_region	Exon 1 of 17	ENSP00000353552.5	P61978-1
	HNRNPK	ENST00000376263.8	TSL:1 MANE Select	c.-110G>A		5_prime_UTR	Exon 1 of 17	ENSP00000365439.3	P61978-2

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46455 AN: 151988 Hom.: 7546 Cov.: 33

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.309

GnomAD4 exome AF: 0.299 AC: 83 AN: 278 Hom.: 11 Cov.: 0 AF XY: 0.278 AC XY: 59 AN XY: 212

African (AFR) AF: 0.833 AC: 5 AN: 6

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 0.375 AC: 3 AN: 8

South Asian (SAS) AF: 0.375 AC: 3 AN: 8

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.257 AC: 59 AN: 230

Other (OTH) AF: 0.563 AC: 9 AN: 16

GnomAD4 genome AF: 0.306 AC: 46495 AN: 152108 Hom.: 7550 Cov.: 33 AF XY: 0.307 AC XY: 22807 AN XY: 74350

African (AFR) AF: 0.420 AC: 17430 AN: 41500

American (AMR) AF: 0.216 AC: 3300 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 975 AN: 3470

East Asian (EAS) AF: 0.268 AC: 1376 AN: 5142

South Asian (SAS) AF: 0.365 AC: 1759 AN: 4822

European-Finnish (FIN) AF: 0.255 AC: 2696 AN: 10588

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18048 AN: 67970

Other (OTH) AF: 0.312 AC: 659 AN: 2110

Alfa AF: 0.278 Hom.: 7299

Bravo AF: 0.303

Asia WGS AF: 0.313 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.84
PhyloP100		0.17
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=297/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.014
SpliceAI score (max)		0.16		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: rs296887; hg19: chr9-86595070;