10-43386473-A-G

Variant names:

• chr10-43386473-A-G
• rs10409
• NM_001098204.2:c.*164T>C

Variant summary

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

The NM_001098204.2(HNRNPF):​c.*164T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0591 in 642,706 control chromosomes in the GnomAD database, including 1,720 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.069 (496 hom., cov: 33)
  • Exomes 𝑓: 0.056 (1224 hom.)
• Consequence: HNRNPF NM_001098204.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.29
• Publications: 8 publications found

Genes affected

HNRNPF (HGNC:5039): (heterogeneous nuclear ribonucleoprotein F) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins that complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and regulate alternative splicing, polyadenylation, 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 has three repeats of quasi-RRM domains that bind to RNAs which have guanosine-rich sequences. This protein is very similar to the family member hnRPH. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098204.2. 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
	HNRNPF	NM_001098204.2	MANE Select	c.*164T>C		3_prime_UTR	Exon 4 of 4	NP_001091674.1
	HNRNPF	NM_001098205.2		c.*164T>C		3_prime_UTR	Exon 4 of 4	NP_001091675.1
	HNRNPF	NM_001098206.2		c.*164T>C		3_prime_UTR	Exon 4 of 4	NP_001091676.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPF	ENST00000682386.1	MANE Select	c.*164T>C		3_prime_UTR	Exon 4 of 4	ENSP00000507787.1
	HNRNPF	ENST00000337970.7	TSL:1	c.*164T>C		3_prime_UTR	Exon 4 of 4	ENSP00000338477.3
	HNRNPF	ENST00000357065.8	TSL:1	c.*164T>C		3_prime_UTR	Exon 4 of 4	ENSP00000349573.4

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 10448 AN: 152194 Hom.: 492 Cov.: 33

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0961

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0376

Gnomad OTH AF: 0.0649

GnomAD4 exome AF: 0.0561 AC: 27500 AN: 490394 Hom.: 1224 Cov.: 6 AF XY: 0.0567 AC XY: 14481 AN XY: 255584

African (AFR) AF: 0.0929 AC: 1245 AN: 13402

American (AMR) AF: 0.0922 AC: 1745 AN: 18932

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 455 AN: 13372

East Asian (EAS) AF: 0.180 AC: 5713 AN: 31776

South Asian (SAS) AF: 0.0814 AC: 2702 AN: 33180

European-Finnish (FIN) AF: 0.0750 AC: 2364 AN: 31526

Middle Eastern (MID) AF: 0.0434 AC: 94 AN: 2166

European-Non Finnish (NFE) AF: 0.0365 AC: 11638 AN: 319194

Other (OTH) AF: 0.0575 AC: 1544 AN: 26846

GnomAD4 genome AF: 0.0688 AC: 10474 AN: 152312 Hom.: 496 Cov.: 33 AF XY: 0.0732 AC XY: 5452 AN XY: 74474

African (AFR) AF: 0.0937 AC: 3894 AN: 41574

American (AMR) AF: 0.0967 AC: 1478 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0325 AC: 113 AN: 3472

East Asian (EAS) AF: 0.199 AC: 1031 AN: 5188

South Asian (SAS) AF: 0.0919 AC: 444 AN: 4830

European-Finnish (FIN) AF: 0.0754 AC: 800 AN: 10604

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0376 AC: 2558 AN: 68034

Other (OTH) AF: 0.0652 AC: 138 AN: 2116

Alfa AF: 0.0461 Hom.: 239

Bravo AF: 0.0710

Asia WGS AF: 0.145 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.92
PhyloP100		3.3
Mutation Taster		=100/0	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: rs10409; hg19: chr10-43881921;