chr9-83978399-G-C

Variant names:

• chr9-83978399-G-C
• rs167203
• NM_031263.4:c.-54C>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_031263.4(HNRNPK):​c.-54C>G variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.86
• Publications: 14 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 Gene-Disease associations (from GenCC):

• Au-Kline syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -18 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 VariationId is 1285706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 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.-54C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 17	NP_112553.1	P61978-2
	HNRNPK	NM_031263.4	MANE Select	c.-54C>G		5_prime_UTR	Exon 2 of 17	NP_112553.1	P61978-2
	HNRNPK	NM_002140.5		c.-54C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 17	NP_002131.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPK	ENST00000376263.8	TSL:1 MANE Select	c.-54C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 17	ENSP00000365439.3	P61978-2
	HNRNPK	ENST00000376281.8	TSL:1	c.-54C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 17	ENSP00000365458.4	P61978-2
	HNRNPK	ENST00000360384.9	TSL:1	c.-54C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 17	ENSP00000353552.5	P61978-1

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

African (AFR) AF: 0.243 AC: 6710 AN: 27596

American (AMR) AF: 0.121 AC: 2147 AN: 17696

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 3883 AN: 18812

East Asian (EAS) AF: 0.000548 AC: 19 AN: 34678

South Asian (SAS) AF: 0.227 AC: 13445 AN: 59160

European-Finnish (FIN) AF: 0.205 AC: 7356 AN: 35908

Middle Eastern (MID) AF: 0.285 AC: 1009 AN: 3542

European-Non Finnish (NFE) AF: 0.215 AC: 219939 AN: 1024850

Other (OTH) AF: 0.202 AC: 10628 AN: 52514

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

African (AFR) AF: 0.249 AC: 10205 AN: 40960

American (AMR) AF: 0.158 AC: 2401 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 704 AN: 3462

East Asian (EAS) AF: 0.00137 AC: 7 AN: 5098

South Asian (SAS) AF: 0.206 AC: 978 AN: 4754

European-Finnish (FIN) AF: 0.215 AC: 2142 AN: 9948

Middle Eastern (MID) AF: 0.288 AC: 83 AN: 288

European-Non Finnish (NFE) AF: 0.221 AC: 14969 AN: 67728

Other (OTH) AF: 0.220 AC: 459 AN: 2086

Alfa AF: 0.223 Hom.: 506

Bravo AF: 0.207

Asia WGS AF: 0.0920 AC: 322 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.89
PhyloP100		1.9
PromoterAI		-0.0068	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs167203; hg19: chr9-86593314; COSMIC: COSV57935884; COSMIC: COSV57935884;