NM_032322.4:c.857_858delGCinsAT

Variant names:

• chr17-30998749-GC-AT
• NM_032322.4:c.857_858delGCinsAT
• RNF135 p.Arg286His

Variant summary

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

The NM_032322.4(RNF135):​c.857_858delGCinsAT​(p.Arg286His) 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. R286C) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF135 NM_032322.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 0 publications found

Genes affected

RNF135 (HGNC:21158): (ring finger protein 135) The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. This gene is located in a chromosomal region known to be frequently deleted in patients with neurofibromatosis. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

RNF135 Gene-Disease associations (from GenCC):

• overgrowth-macrocephaly-facial dysmorphism syndrome

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• overgrowth syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000298294 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032322.4. 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
	RNF135	NM_032322.4	MANE Select	c.857_858delGCinsAT	p.Arg286His	missense	N/A	NP_115698.3
	RNF135	NM_001184992.2		c.*61_*62delGCinsAT		3_prime_UTR	Exon 6 of 6	NP_001171921.1	Q8IUD6-3
	RNF135	NM_197939.2		c.*61_*62delGCinsAT		3_prime_UTR	Exon 4 of 4	NP_922921.1	Q8IUD6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF135	ENST00000328381.10	TSL:1 MANE Select	c.857_858delGCinsAT	p.Arg286His	missense	N/A	ENSP00000328340.5	Q8IUD6-1
	RNF135	ENST00000535306.6	TSL:1	c.*61_*62delGCinsAT		3_prime_UTR	Exon 6 of 6	ENSP00000440470.2	Q8IUD6-3
	RNF135	ENST00000324689.8	TSL:1	c.*61_*62delGCinsAT		3_prime_UTR	Exon 4 of 4	ENSP00000323693.4	Q8IUD6-2

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		-0.17

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: chr17-29325767;