rs748770068

Variant names:

• chr20-57407794-C-G
• rs748770068
• NM_017495.6:c.668C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-57407794-C-G
• chr20-57407794-C-T

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.668C>G​(p.Thr223Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000612 in 1,601,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: RBM38 NM_017495.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.27
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.100328565).

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.668C>G	p.Thr223Ser	missense	Exon 4 of 4	NP_059965.2
	RBM38	NM_001291780.2		c.764C>G	p.Thr255Ser	missense	Exon 5 of 5	NP_001278709.1
	RBM38	NM_183425.3		c.*247C>G		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.668C>G	p.Thr223Ser	missense	Exon 4 of 4	ENSP00000348538.5	Q9H0Z9-1
	RBM38	ENST00000371219.2	TSL:2	c.425C>G	p.Thr142Ser	missense	Exon 4 of 4	ENSP00000360263.2	A6NG75
	RBM38	ENST00000344785.10	TSL:5	c.*268C>G		3_prime_UTR	Exon 5 of 5	ENSP00000345248.6	F6VZ39

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152248 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

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: 0.0000180 AC: 4 AN: 221786 AF XY: 0.0000246

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: 0.0000401

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000662 AC: 96 AN: 1449208 Hom.: 0 Cov.: 32 AF XY: 0.0000722 AC XY: 52 AN XY: 720352

African (AFR) AF: 0.00 AC: 0 AN: 33286

American (AMR) AF: 0.00 AC: 0 AN: 43224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25806

East Asian (EAS) AF: 0.00 AC: 0 AN: 39258

South Asian (SAS) AF: 0.00 AC: 0 AN: 84912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000866 AC: 96 AN: 1108032

Other (OTH) AF: 0.00 AC: 0 AN: 59956

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152248 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74386

African (AFR) AF: 0.0000241 AC: 1 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

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: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000566 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000832 AC: 1

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	0.071
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.18
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.3
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.11
Sift	Benign	0.11	T
Sift4G	Benign	0.85	T
Polyphen		0.13	B
Vest4		0.12
MutPred		0.26		Loss of glycosylation at T224 (P = 0.166)
MVP		0.29
MPC		0.090
ClinPred		0.30	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.36
Mutation Taster		=90/10	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: rs748770068; hg19: chr20-55982850;