RBM38 p.Thr223Ser

Variant names:

• chr20-57407793-A-T
• NM_017495.6:c.667A>T
• RBM38 p.Thr223Ser

Your query was ambiguous. Multiple possible variants found:

• chr20-57407793-A-T
• chr20-57407794-C-G
• chr20-57407793-ACC-TCT
• chr20-57407793-ACC-TCA
• chr20-57407793-ACC-TCG
• chr20-57407794-CC-GT

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.667A>T​(p.Thr223Ser) 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. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: RBM38 NM_017495.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• 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=0.07207975).

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.667A>T	p.Thr223Ser	missense	Exon 4 of 4	NP_059965.2
	RBM38	NM_001291780.2		c.763A>T	p.Thr255Ser	missense	Exon 5 of 5	NP_001278709.1
	RBM38	NM_183425.3		c.*246A>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.667A>T	p.Thr223Ser	missense	Exon 4 of 4	ENSP00000348538.5	Q9H0Z9-1
	RBM38	ENST00000371219.2	TSL:2	c.424A>T	p.Thr142Ser	missense	Exon 4 of 4	ENSP00000360263.2	A6NG75
	RBM38	ENST00000344785.10	TSL:5	c.*267A>T		3_prime_UTR	Exon 5 of 5	ENSP00000345248.6	F6VZ39

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.17
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.015
Sift	Benign	0.11	T
Sift4G	Benign	0.85	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.026
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-55982849;