17-4940973-A-C

Position:

• chr17-4940973-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015528.3(RNF167):​c.64A>C​(p.Thr22Pro) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF167 NM_015528.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.142

Genes affected

RNF167 (HGNC:24544): (ring finger protein 167) RNF167 is an E3 ubiquitin ligase that interacts with TSSC5 (SLC22A18; MIM 602631) and, together with UBCH6 (UBE2E1; MIM 602916), facilitates TSSC5 polyubiquitylation (Yamada and Gorbsky, 2006 [PubMed 16314844]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14699665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF167	NM_015528.3	c.64A>C	p.Thr22Pro	missense_variant	2/10	ENST00000262482.11	NP_056343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF167	ENST00000262482.11	c.64A>C	p.Thr22Pro	missense_variant	2/10	2	NM_015528.3	ENSP00000262482.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.64A>C (p.T22P) alteration is located in exon 2 (coding exon 1) of the RNF167 gene. This alteration results from a A to C substitution at nucleotide position 64, causing the threonine (T) at amino acid position 22 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.87
DEOGEN2	Benign	0.043	T;T;T;T;T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.50	.;T;T;.;.;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.15	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.;.;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.7	.;.;.;.;N;.
REVEL	Benign	0.12
Sift	Benign	0.11	.;.;.;.;T;.
Sift4G	Benign	0.30	T;T;T;T;T;T
Polyphen		0.90	P;.;.;P;P;P
Vest4		0.27
MutPred		0.44		Gain of catalytic residue at P21 (P = 0.017);Gain of catalytic residue at P21 (P = 0.017);Gain of catalytic residue at P21 (P = 0.017);Gain of catalytic residue at P21 (P = 0.017);Gain of catalytic residue at P21 (P = 0.017);Gain of catalytic residue at P21 (P = 0.017);
MVP		0.26
MPC		0.078
ClinPred		0.49	T
GERP RS		-4.2
Varity_R		0.29
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-4844268;