chr17-76158415-G-C

Variant names:

• chr17-76158415-G-C
• rs61751845
• NM_052916.3:c.1391C>G

Variant summary

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

The NM_052916.3(RNF157):​c.1391C>G​(p.Pro464Arg) 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. 16/22 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. P464L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF157 NM_052916.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277
• Publications: 8 publications found

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]

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=0.025804192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF157	NM_052916.3	c.1391C>G	p.Pro464Arg	missense_variant	Exon 13 of 19	ENST00000269391.11	NP_443148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF157	ENST00000269391.11	c.1391C>G	p.Pro464Arg	missense_variant	Exon 13 of 19	1	NM_052916.3	ENSP00000269391.4
RNF157	ENST00000647930.1	c.1391C>G	p.Pro464Arg	missense_variant	Exon 13 of 19			ENSP00000497353.1
RNF157	ENST00000319945.10	c.1391C>G	p.Pro464Arg	missense_variant	Exon 13 of 18	2		ENSP00000321837.4
RNF157	ENST00000592869.1	n.109C>G		non_coding_transcript_exon_variant	Exon 1 of 5	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251160 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.15
DANN	Benign	0.83
DEOGEN2	Benign	0.013	T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.026	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.69	N;.;N
PhyloP100		-0.28
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.7	N;.;N
REVEL	Benign	0.014
Sift	Benign	0.64	T;.;T
Sift4G	Benign	0.47	T;.;T
Polyphen		0.0	B;.;B
Vest4		0.085
MutPred		0.22		Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);
MVP		0.23
MPC		0.14
ClinPred		0.025	T
GERP RS		-0.30
Varity_R		0.035
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs61751845; hg19: chr17-74154496;