1-161154065-GA-AG

Variant names:

• chr1-161154065-GA-AG
• NM_016406.4:c.68_69delGAinsAG
• UFC1 p.Arg23Gln

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PS1 PP2 PP3

The NM_016406.4(UFC1):​c.68_69delGAinsAG​(p.Arg23Gln) variant causes a missense change involving the alteration of a 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 Pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UFC1 NM_016406.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.81
• Publications: 0 publications found

Genes affected

UFC1 (HGNC:26941): (ubiquitin-fold modifier conjugating enzyme 1) UFC1 is an E2-like conjugating enzyme for ubiquitin-fold modifier-1 (UFM1; MIM 610553) (Komatsu et al., 2004 [PubMed 15071506]).[supplied by OMIM, Mar 2008]

UFC1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with spasticity and poor growth

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000224985 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PS1: Transcript NM_016406.4 (UFC1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.23442 (below the threshold of 3.09). Trascript score misZ: 0.76313 (below the threshold of 3.09). GenCC associations: The gene is linked to neurodevelopmental disorder with spasticity and poor growth.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016406.4. 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
	UFC1	NM_016406.4	MANE Select	c.68_69delGAinsAG	p.Arg23Gln	missense	N/A	NP_057490.2	Q9Y3C8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFC1	ENST00000368003.6	TSL:1 MANE Select	c.68_69delGAinsAG	p.Arg23Gln	missense	N/A	ENSP00000356982.5	Q9Y3C8
	UFC1	ENST00000482672.1	TSL:1	n.81_82delGAinsAG		non_coding_transcript_exon	Exon 1 of 2
	UFC1	ENST00000913804.1		c.68_69delGAinsAG	p.Arg23Gln	missense	N/A	ENSP00000583863.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.8

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: chr1-161123855;