NM_022781.5:c.694G>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26385838).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022781.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF38	NM_022781.5	MANE Select	c.694G>A	p.Val232Ile	missense	Exon 5 of 12	NP_073618.3
	RNF38	NM_194329.3		c.544G>A	p.Val182Ile	missense	Exon 4 of 11	NP_919310.1	Q9H0F5-2
	RNF38	NM_194328.3		c.445G>A	p.Val149Ile	missense	Exon 5 of 12	NP_919309.1	Q9H0F5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF38	ENST00000259605.11	TSL:1 MANE Select	c.694G>A	p.Val232Ile	missense	Exon 5 of 12	ENSP00000259605.6	Q9H0F5-1
	RNF38	ENST00000353739.8	TSL:1	c.544G>A	p.Val182Ile	missense	Exon 4 of 11	ENSP00000335239.5	Q9H0F5-2
	RNF38	ENST00000377877.4	TSL:2	c.466G>A	p.Val156Ile	missense	Exon 5 of 12	ENSP00000367109.3	Q9H0F5-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.14
Sift	Uncertain	0.013	D
Sift4G	Benign	0.30	T
Polyphen		0.63	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
Mutation Taster		=91/9	polymorphism

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

hg19: chr9-36357816;