chr17-30971429-GC-AA

Variant names:

• chr17-30971429-GC-AA
• rs797045917
• NM_032322.4:c.356_357delGCinsAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_032322.4(RNF135):​c.356_357delGCinsAA​(p.Arg119Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.0000787 in 11 alleles, including 0 homozygotes. 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R119C) has been classified as Uncertain significance.

• Frequency: GnomAD MNV: 𝑓 0.000079 Genomes: not found (cov: 33)
• Consequence: RNF135 NM_032322.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.186
• 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

ENSG00000264456 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdMnv at 11 AD gene.

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.356_357delGCinsAA	p.Arg119Gln	missense	N/A	NP_115698.3
	RNF135	NM_001184992.2		c.356_357delGCinsAA	p.Arg119Gln	missense	N/A	NP_001171921.1	Q8IUD6-3
	RNF135	NM_197939.2		c.356_357delGCinsAA	p.Arg119Gln	missense	N/A	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.356_357delGCinsAA	p.Arg119Gln	missense	N/A	ENSP00000328340.5	Q8IUD6-1
	RNF135	ENST00000535306.6	TSL:1	c.356_357delGCinsAA	p.Arg119Gln	missense	N/A	ENSP00000440470.2	Q8IUD6-3
	RNF135	ENST00000324689.8	TSL:1	c.356_357delGCinsAA	p.Arg119Gln	missense	N/A	ENSP00000323693.4	Q8IUD6-2

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

GnomAD MNV AF: 0.0000787 AC: 11 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs797045917; hg19: chr17-29298447;