9-83969444-TAAAAG-T

Variant names:

• chr9-83969444-TAAAAG-T
• rs746640216
• NM_031263.4:c.1362-9_1362-5delCTTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_031263.4(HNRNPK):​c.1362-9_1362-5delCTTTT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0000312 in 1,570,190 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: HNRNPK NM_031263.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.19
• 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)

ACMG classification

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

• BP6: Variant 9-83969444-TAAAAG-T is Benign according to our data. Variant chr9-83969444-TAAAAG-T is described in ClinVar as Likely_benign. ClinVar VariationId is 717027.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000591 (9/152168) while in subpopulation AFR AF = 0.000145 (6/41508). AF 95% confidence interval is 0.0000627. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 9 AD gene.

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.1362-9_1362-5delCTTTT		splice_region intron	N/A	NP_112553.1	P61978-2
	HNRNPK	NM_002140.5		c.1362-9_1362-5delCTTTT		splice_region intron	N/A	NP_002131.2
	HNRNPK	NM_001318188.2		c.1362-69_1362-65delCTTTT		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.1362-9_1362-5delCTTTT		splice_region intron	N/A	ENSP00000365439.3	P61978-2
	HNRNPK	ENST00000376281.8	TSL:1	c.1362-9_1362-5delCTTTT		splice_region intron	N/A	ENSP00000365458.4	P61978-2
	HNRNPK	ENST00000360384.9	TSL:1	c.1362-69_1362-65delCTTTT		intron	N/A	ENSP00000353552.5	P61978-1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000357 AC: 8 AN: 223912 AF XY: 0.0000163

Gnomad AFR exome AF: 0.000211

Gnomad AMR exome AF: 0.0000350

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000118

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000195

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000282 AC: 40 AN: 1418022 Hom.: 0 AF XY: 0.0000255 AC XY: 18 AN XY: 706804

African (AFR) AF: 0.0000319 AC: 1 AN: 31366

American (AMR) AF: 0.0000262 AC: 1 AN: 38128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24970

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39506

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81330

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 0.0000304 AC: 33 AN: 1085780

Other (OTH) AF: 0.0000170 AC: 1 AN: 58698

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74396

African (AFR) AF: 0.000145 AC: 6 AN: 41508

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

EpiCase AF: 0.0000546

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely 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		6.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs746640216; hg19: chr9-86584359; COSMIC: COSV61088742; COSMIC: COSV61088742;