19-8445104-CCT-GCG

Variant names:

• chr19-8445104-CCT-GCG
• NM_005968.5:c.106_108delCCTinsGCG
• HNRNPM p.Pro36Ala

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005968.5(HNRNPM):​c.106_108delCCTinsGCG​(p.Pro36Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P36S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HNRNPM NM_005968.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26
• Publications: 0 publications found

Genes affected

HNRNPM (HGNC:5046): (heterogeneous nuclear ribonucleoprotein M) 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 has three repeats of quasi-RRM domains that bind to RNAs. This protein also constitutes a monomer of the N-acetylglucosamine-specific receptor which is postulated to trigger selective recycling of immature GlcNAc-bearing thyroglobulin molecules. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ENSG00000279827 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005968.5. 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
	HNRNPM	NM_005968.5	MANE Select	c.106_108delCCTinsGCG	p.Pro36Ala	missense	N/A	NP_005959.2
	HNRNPM	NM_031203.4		c.106_108delCCTinsGCG	p.Pro36Ala	missense	N/A	NP_112480.2	P52272-2
	HNRNPM	NM_001297418.2		c.-202_-200delCCTinsGCG		5_prime_UTR	Exon 1 of 14	NP_001284347.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPM	ENST00000325495.9	TSL:1 MANE Select	c.106_108delCCTinsGCG	p.Pro36Ala	missense	N/A	ENSP00000325376.2	P52272-1
	HNRNPM	ENST00000348943.7	TSL:1	c.106_108delCCTinsGCG	p.Pro36Ala	missense	N/A	ENSP00000325732.2	P52272-2
	HNRNPM	ENST00000940928.1		c.106_108delCCTinsGCG	p.Pro36Ala	missense	N/A	ENSP00000610987.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

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

hg19: chr19-8509988;