17-76154320-A-T

Position:

• chr17-76154320-A-T

Variant summary

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

The NM_052916.3(RNF157):​c.1773T>A​(p.Asp591Glu) 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. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF157 NM_052916.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.92

Genes affected

RNF157 (HGNC:29402): (ring finger protein 157) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in several processes, including negative regulation of signal transduction; positive regulation of dendrite extension; and protein autoubiquitination. Predicted to be located in cell body. Predicted to be active in early endosome; nucleus; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RNF157 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF157	NM_052916.3	c.1773T>A	p.Asp591Glu	missense_variant	17/19	ENST00000269391.11	NP_443148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF157	ENST00000269391.11	c.1773T>A	p.Asp591Glu	missense_variant	17/19	1	NM_052916.3	ENSP00000269391.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

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

May 31, 2023

The c.1773T>A (p.D591E) alteration is located in exon 17 (coding exon 17) of the RNF157 gene. This alteration results from a T to A substitution at nucleotide position 1773, causing the aspartic acid (D) at amino acid position 591 to be replaced by a glutamic acid (E). 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	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0086	T;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.85	T;D;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	0.90	L;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.97	N;.;N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D;.;D
Sift4G	Uncertain	0.011	D;.;T
Polyphen		0.99	D;.;P
Vest4		0.21
MutPred		0.19		Gain of solvent accessibility (P = 0.0638);Gain of solvent accessibility (P = 0.0638);.;
MVP		0.36
MPC		0.21
ClinPred		0.61	D
GERP RS		-10
Varity_R		0.49
gMVP		0.045

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: -37

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: chr17-74150401;