17-30971310-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_032322.4(RNF135):c.237G>A(p.Gln79=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000287 in 1,533,904 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000025 (1 hom.)
• Consequence: RNF135 NM_032322.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-30971310-G-A is Benign according to our data. Variant chr17-30971310-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 725172.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.13 with no splicing effect.
• BS2: High AC in GnomAd at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF135	NM_032322.4	c.237G>A	p.Gln79=	synonymous_variant	1/5	ENST00000328381.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF135	ENST00000328381.10	c.237G>A	p.Gln79=	synonymous_variant	1/5	1	NM_032322.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000167 AC: 21 AN: 125786 Hom.: 1 AF XY: 0.000187 AC XY: 13 AN XY: 69372

Gnomad AFR exome AF: 0.000285

Gnomad AMR exome AF: 0.000800

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000219

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000253 AC: 35 AN: 1381582 Hom.: 1 Cov.: 31 AF XY: 0.0000293 AC XY: 20 AN XY: 682008

Gnomad4 AFR exome AF: 0.0000688

Gnomad4 AMR exome AF: 0.000597

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000102

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152322 Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5 AN XY: 74480

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000642

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	8.9
Dann	Benign	0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs574502925; hg19: chr17-29298328;