chr9-36357819-C-T

Variant names:

• chr9-36357819-C-T
• NM_022781.5:c.694G>A

Variant summary

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

The NM_022781.5(RNF38):​c.694G>A​(p.Val232Ile) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF38 NM_022781.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.94

Genes affected

RNF38 (HGNC:18052): (ring finger protein 38) This gene encodes a protein with a coiled-coil motif and a RING-H2 motif (C3H2C2) at its carboxy-terminus. The RING motif is a zinc-binding domain found in a large set of proteins playing roles in diverse cellular processes including oncogenesis, development, signal transduction, and apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 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=0.26385838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF38	NM_022781.5	c.694G>A	p.Val232Ile	missense_variant	Exon 5 of 12	ENST00000259605.11	NP_073618.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF38	ENST00000259605.11	c.694G>A	p.Val232Ile	missense_variant	Exon 5 of 12	1	NM_022781.5	ENSP00000259605.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.694G>A (p.V232I) alteration is located in exon 5 (coding exon 5) of the RNF38 gene. This alteration results from a G to A substitution at nucleotide position 694, causing the valine (V) at amino acid position 232 to be replaced by an isoleucine (I). 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	0.090
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T;.;.;.;.;.;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T;T;T;.;.;T;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T;T;T;T;T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.55	N;.;.;.;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.36	N;N;.;N;N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.013	D;D;.;D;D;D;D
Sift4G	Benign	0.30	T;T;T;T;T;T;T
Polyphen		0.63	P;P;.;.;.;.;.
Vest4		0.28
MutPred		0.27		Gain of sheet (P = 0.039);.;.;.;.;.;.;
MVP		0.37
MPC		0.45
ClinPred		0.57	D
GERP RS		6.0
Varity_R		0.10
gMVP		0.19

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-36357816;