20-57391643-C-G

Variant names:

• chr20-57391643-C-G
• rs371553583
• NM_017495.6:c.62C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017495.6(RBM38):​c.62C>G​(p.Pro21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,477,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P21L) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: RBM38 NM_017495.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 1 publications found

Genes affected

RBM38 (HGNC:15818): (RNA binding motif protein 38) Enables mRNA 3'-UTR binding activity. Involved in DNA damage response, signal transduction by p53 class mediator; negative regulation of cell population proliferation; and regulation of RNA metabolic process. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RBM38-AS1 (HGNC:40725): (RBM38 antisense RNA 1)

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=0.16537523).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017495.6. 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
	RBM38	NM_017495.6	MANE Select	c.62C>G	p.Pro21Arg	missense	Exon 1 of 4	NP_059965.2
	RBM38	NM_001291780.2		c.62C>G	p.Pro21Arg	missense	Exon 1 of 5	NP_001278709.1
	RBM38	NM_183425.3		c.62C>G	p.Pro21Arg	missense	Exon 1 of 3	NP_906270.1	Q9H0Z9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM38	ENST00000356208.10	TSL:1 MANE Select	c.62C>G	p.Pro21Arg	missense	Exon 1 of 4	ENSP00000348538.5	Q9H0Z9-1
	RBM38	ENST00000440234.6	TSL:2	c.62C>G	p.Pro21Arg	missense	Exon 1 of 3	ENSP00000407848.2	Q9H0Z9-2
	RBM38	ENST00000344785.10	TSL:5	c.-8C>G		5_prime_UTR	Exon 1 of 5	ENSP00000345248.6	F6VZ39

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150386 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000678 AC: 9 AN: 1327280 Hom.: 0 Cov.: 31 AF XY: 0.00000458 AC XY: 3 AN XY: 654910

African (AFR) AF: 0.00 AC: 0 AN: 26758

American (AMR) AF: 0.00 AC: 0 AN: 28786

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22838

East Asian (EAS) AF: 0.00 AC: 0 AN: 28404

South Asian (SAS) AF: 0.00 AC: 0 AN: 73660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46812

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5184

European-Non Finnish (NFE) AF: 0.00000865 AC: 9 AN: 1040858

Other (OTH) AF: 0.00 AC: 0 AN: 53980

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150386 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73400

African (AFR) AF: 0.00 AC: 0 AN: 41258

American (AMR) AF: 0.00 AC: 0 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67502

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.10
Sift	Benign	0.041	D
Sift4G	Benign	0.16	T
Polyphen		0.56	P
Vest4		0.042
MutPred		0.25		Gain of methylation at P21 (P = 0.0493)
MVP		0.31
MPC		1.1
ClinPred		0.13	T
GERP RS		-0.26
PromoterAI		0.00020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.094
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

dbSNP: rs371553583; hg19: chr20-55966699;