9-36356455-C-G

Variant names:

• chr9-36356455-C-G
• rs769462459
• NM_022781.5:c.757G>C

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.757G>C​(p.Val253Leu) 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. 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. V253I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: RNF38 NM_022781.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00
• 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=0.23178607).

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.757G>C	p.Val253Leu	missense	Exon 6 of 12	NP_073618.3
	RNF38	NM_194329.3		c.607G>C	p.Val203Leu	missense	Exon 5 of 11	NP_919310.1	Q9H0F5-2
	RNF38	NM_194328.3		c.508G>C	p.Val170Leu	missense	Exon 6 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.757G>C	p.Val253Leu	missense	Exon 6 of 12	ENSP00000259605.6	Q9H0F5-1
	RNF38	ENST00000353739.8	TSL:1	c.607G>C	p.Val203Leu	missense	Exon 5 of 11	ENSP00000335239.5	Q9H0F5-2
	RNF38	ENST00000377877.4	TSL:2	c.529G>C	p.Val177Leu	missense	Exon 6 of 12	ENSP00000367109.3	Q9H0F5-4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.0
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.072
Sift	Uncertain	0.025	D
Sift4G	Benign	0.41	T
Polyphen		0.43	B
Vest4		0.46
MutPred		0.21		Loss of loop (P = 0.0112)
MVP		0.21
MPC		0.44
ClinPred		0.44	T
GERP RS		5.9
Varity_R		0.14
gMVP		0.29
Mutation Taster		=67/33	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

dbSNP: rs769462459; hg19: chr9-36356452;