rs1364910406

Variant names:

• chr17-30971211-G-A
• rs1364910406
• NM_032322.4:c.138G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-30971211-G-A
• chr17-30971211-G-C
• chr17-30971211-G-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_032322.4(RNF135):​c.138G>A​(p.Glu46Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000514 in 1,361,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: RNF135 NM_032322.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• 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

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-0.31 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF135	NM_032322.4	c.138G>A	p.Glu46Glu	synonymous_variant	Exon 1 of 5	ENST00000328381.10	NP_115698.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF135	ENST00000328381.10	c.138G>A	p.Glu46Glu	synonymous_variant	Exon 1 of 5	1	NM_032322.4	ENSP00000328340.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000183 AC: 2 AN: 109160 AF XY: 0.0000164

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000458

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000246

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000514 AC: 7 AN: 1361426 Hom.: 0 Cov.: 31 AF XY: 0.00000745 AC XY: 5 AN XY: 671504

African (AFR) AF: 0.00 AC: 0 AN: 27866

American (AMR) AF: 0.0000303 AC: 1 AN: 33048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24174

East Asian (EAS) AF: 0.0000301 AC: 1 AN: 33224

South Asian (SAS) AF: 0.00 AC: 0 AN: 76868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4562

European-Non Finnish (NFE) AF: 0.00000467 AC: 5 AN: 1070222

Other (OTH) AF: 0.00 AC: 0 AN: 56706

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.85
PhyloP100		-0.31
PromoterAI		-0.12	Neutral

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

Other links and lift over

dbSNP: rs1364910406; hg19: chr17-29298229;