20-57407707-C-T

Variant names:

• chr20-57407707-C-T
• rs1047780022
• NM_017495.6:c.581C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017495.6(RBM38):​c.581C>T​(p.Ala194Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,611,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: RBM38 NM_017495.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.14
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31325352).

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.581C>T	p.Ala194Val	missense	Exon 4 of 4	NP_059965.2
	RBM38	NM_001291780.2		c.677C>T	p.Ala226Val	missense	Exon 5 of 5	NP_001278709.1
	RBM38	NM_183425.3		c.*160C>T		3_prime_UTR	Exon 3 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.581C>T	p.Ala194Val	missense	Exon 4 of 4	ENSP00000348538.5	Q9H0Z9-1
	RBM38	ENST00000371219.2	TSL:2	c.338C>T	p.Ala113Val	missense	Exon 4 of 4	ENSP00000360263.2	A6NG75
	RBM38	ENST00000344785.10	TSL:5	c.*181C>T		3_prime_UTR	Exon 5 of 5	ENSP00000345248.6	F6VZ39

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152258 Hom.: 0 Cov.: 34

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 243634 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000911

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000617 AC: 9 AN: 1459728 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 726260

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51808

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111696

Other (OTH) AF: 0.0000166 AC: 1 AN: 60260

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152258 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74392

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

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	0.18
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.16
Sift	Benign	0.14	T
Sift4G	Benign	0.15	T
Polyphen		0.73	P
Vest4		0.51
MutPred		0.26		Loss of disorder (P = 0.065)
MVP		0.33
MPC		0.12
ClinPred		0.56	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.80
Mutation Taster		=66/34	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: rs1047780022; hg19: chr20-55982763;