20-57391643-C-A

Variant names:

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

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>A​(p.Pro21His) 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. 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. P21L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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=0.23831627).

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>A	p.Pro21His	missense	Exon 1 of 4	NP_059965.2
	RBM38	NM_001291780.2		c.62C>A	p.Pro21His	missense	Exon 1 of 5	NP_001278709.1
	RBM38	NM_183425.3		c.62C>A	p.Pro21His	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>A	p.Pro21His	missense	Exon 1 of 4	ENSP00000348538.5	Q9H0Z9-1
	RBM38	ENST00000440234.6	TSL:2	c.62C>A	p.Pro21His	missense	Exon 1 of 3	ENSP00000407848.2	Q9H0Z9-2
	RBM38	ENST00000344785.10	TSL:5	c.-8C>A		5_prime_UTR	Exon 1 of 5	ENSP00000345248.6	F6VZ39

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1327280 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 1040858

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.59	T
M_CAP	Pathogenic	0.93	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.16
Sift	Uncertain	0.019	D
Sift4G	Benign	0.084	T
Polyphen		0.93	P
Vest4		0.14
MutPred		0.22		Gain of catalytic residue at P21 (P = 0.093)
MVP		0.37
MPC		1.5
ClinPred		0.37	T
GERP RS		-0.26
PromoterAI		-0.073	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.16
gMVP		0.19
Mutation Taster		=92/8	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;