chr20-57391643-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_017495.6(RBM38):​c.62C>T​(p.Pro21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000556 in 1,477,772 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (1 hom.)
• Consequence: RBM38 NM_017495.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004431993).
• BP6: Variant 20-57391643-C-T is Benign according to our data. Variant chr20-57391643-C-T is described in ClinVar as Benign. ClinVar VariationId is 789858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

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>T	p.Pro21Leu	missense	Exon 1 of 4	NP_059965.2
	RBM38	NM_001291780.2		c.62C>T	p.Pro21Leu	missense	Exon 1 of 5	NP_001278709.1
	RBM38	NM_183425.3		c.62C>T	p.Pro21Leu	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>T	p.Pro21Leu	missense	Exon 1 of 4	ENSP00000348538.5	Q9H0Z9-1
	RBM38	ENST00000440234.6	TSL:2	c.62C>T	p.Pro21Leu	missense	Exon 1 of 3	ENSP00000407848.2	Q9H0Z9-2
	RBM38	ENST00000344785.10	TSL:5	c.-8C>T		5_prime_UTR	Exon 1 of 5	ENSP00000345248.6	F6VZ39

Frequencies

GnomAD3 genomes AF: 0.00292 AC: 439 AN: 150386 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00194

GnomAD2 exomes AF: 0.000396 AC: 43 AN: 108560 AF XY: 0.000252

Gnomad AFR exome AF: 0.0123

Gnomad AMR exome AF: 0.000547

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000348

GnomAD4 exome AF: 0.000288 AC: 382 AN: 1327278 Hom.: 1 Cov.: 31 AF XY: 0.000257 AC XY: 168 AN XY: 654910

African (AFR) AF: 0.0116 AC: 310 AN: 26756

American (AMR) AF: 0.000764 AC: 22 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: 0.0000136 AC: 1 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: 0.00000673 AC: 7 AN: 1040858

Other (OTH) AF: 0.000778 AC: 42 AN: 53980

GnomAD4 genome AF: 0.00292 AC: 439 AN: 150494 Hom.: 2 Cov.: 32 AF XY: 0.00302 AC XY: 222 AN XY: 73518

African (AFR) AF: 0.0101 AC: 417 AN: 41376

American (AMR) AF: 0.00106 AC: 16 AN: 15144

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67492

Other (OTH) AF: 0.00192 AC: 4 AN: 2084

Alfa AF: 0.00236 Hom.: 0

ESP6500AA AF: 0.00589 AC: 18

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000335 AC: 23

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.95	N
REVEL	Benign	0.053
Sift	Benign	0.15	T
Sift4G	Benign	0.26	T
Polyphen		0.0030	B
Vest4		0.068
MVP		0.24
MPC		1.1
ClinPred		0.0081	T
GERP RS		-0.26
PromoterAI		0.0072	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.075
gMVP		0.18
Mutation Taster		=93/7	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;