9-36353244-G-A

Variant names:

• chr9-36353244-G-A
• rs145433267
• NM_022781.5:c.997C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_022781.5(RNF38):​c.997C>T​(p.Pro333Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P333T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: RNF38 NM_022781.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.25
• Publications: 5 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13727352).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

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.997C>T	p.Pro333Ser	missense	Exon 7 of 12	NP_073618.3
	RNF38	NM_194329.3		c.847C>T	p.Pro283Ser	missense	Exon 6 of 11	NP_919310.1	Q9H0F5-2
	RNF38	NM_194328.3		c.748C>T	p.Pro250Ser	missense	Exon 7 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.997C>T	p.Pro333Ser	missense	Exon 7 of 12	ENSP00000259605.6	Q9H0F5-1
	RNF38	ENST00000353739.8	TSL:1	c.847C>T	p.Pro283Ser	missense	Exon 6 of 11	ENSP00000335239.5	Q9H0F5-2
	RNF38	ENST00000377877.4	TSL:2	c.769C>T	p.Pro257Ser	missense	Exon 7 of 12	ENSP00000367109.3	Q9H0F5-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251200 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460860 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726778

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.0000671 AC: 3 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111130

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Uncertain	0.97
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	-0.62	N
PhyloP100		6.2
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.13
Sift	Benign	0.078	T
Sift4G	Benign	0.52	T
Polyphen		0.025	B
Vest4		0.48
MutPred		0.32		Gain of relative solvent accessibility (P = 0.0098)
MVP		0.36
MPC		0.40
ClinPred		0.25	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.043
gMVP		0.17
Mutation Taster		=94/6	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: rs145433267; hg19: chr9-36353241;