5-178210162-GC-TT

Variant names:

• chr5-178210162-GC-TT
• NM_031266.3:c.818_819delGCinsTT
• HNRNPAB p.Gly273Val

Variant summary

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

The NM_031266.3(HNRNPAB):​c.818_819delGCinsTT​(p.Gly273Val) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G273D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HNRNPAB NM_031266.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 0 publications found

Genes affected

HNRNPAB (HGNC:5034): (heterogeneous nuclear ribonucleoprotein A/B) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are produced by RNA polymerase II and are components of the heterogeneous nuclear RNA (hnRNA) complexes. They 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, which binds to one of the components of the multiprotein editosome complex, has two repeats of quasi-RRM (RNA recognition motif) domains that bind to RNAs. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

PHYKPL (HGNC:28249): (5-phosphohydroxy-L-lysine phospho-lyase) This is a nuclear gene encoding a mitochondrial enzyme that catalyzes the conversion of 5-phosphonooxy-L-lysine to ammonia, inorganic phosphate, and 2-aminoadipate semialdehyde. Mutations in this gene may cause phosphohydroxylysinuria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

PHYKPL Gene-Disease associations (from GenCC):

• phosphohydroxylysinuria

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031266.3. 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
	HNRNPAB	NM_031266.3	MANE Select	c.818_819delGCinsTT	p.Gly273Val	missense	N/A	NP_112556.2	Q99729-2
	PHYKPL	NM_153373.4	MANE Select	c.*32-1248_*32-1247delGCinsAA		intron	N/A	NP_699204.1	Q8IUZ5-1
	HNRNPAB	NM_001437957.1		c.818_819delGCinsTT	p.Gly273Val	missense	N/A	NP_001424886.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPAB	ENST00000358344.8	TSL:1 MANE Select	c.818_819delGCinsTT	p.Gly273Val	missense	N/A	ENSP00000351108.3	Q99729-2
	HNRNPAB	ENST00000504898.5	TSL:1	c.818_819delGCinsTT	p.Gly273Val	missense	N/A	ENSP00000425031.1	Q99729-2
	PHYKPL	ENST00000308158.10	TSL:1 MANE Select	c.*32-1248_*32-1247delGCinsAA		intron	N/A	ENSP00000310978.5	Q8IUZ5-1

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		2.7

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: chr5-177637163;