rs1167074464

Variant names:

• chr17-30971089-C-A
• rs1167074464
• NM_032322.4:c.16C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-30971089-C-A
• chr17-30971089-C-G
• chr17-30971089-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032322.4(RNF135):​c.16C>A​(p.Leu6Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L6V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF135 NM_032322.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.86
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050117105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF135	NM_032322.4	c.16C>A	p.Leu6Met	missense_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.16C>A	p.Leu6Met	missense_variant	Exon 1 of 5	1	NM_032322.4	ENSP00000328340.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.023
DANN	Benign	0.59
DEOGEN2	Benign	0.0035	T;T;.;.
Eigen	Benign	-2.6
Eigen_PC	Benign	-2.8
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.23	T;T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.050	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.1	N;.;N;N
PhyloP100		-4.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.44	N;N;N;N
REVEL	Benign	0.043
Sift	Benign	0.13	T;D;T;T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.55	P;.;B;.
Vest4		0.11
MutPred		0.67		Gain of disorder (P = 0.0957);Gain of disorder (P = 0.0957);Gain of disorder (P = 0.0957);Gain of disorder (P = 0.0957);
MVP		0.16
MPC		0.086
ClinPred		0.20	T
GERP RS		-7.8
PromoterAI		-0.25	Neutral
Varity_R		0.061
gMVP		0.10

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: rs1167074464; hg19: chr17-29298107;