NM_032120.4:c.8C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032120.4(RBM48):c.8C>T(p.Ser3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,613,860 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 16 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 12 hom. )

Consequence

RBM48
NM_032120.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.227

Variant links:

Genes affected

RBM48 (HGNC:21785): (RNA binding motif protein 48) Predicted to enable RNA binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RBM48 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042303503).

BP6

Variant 7-92528821-C-T is Benign according to our data. Variant chr7-92528821-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 776237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00736 (1121/152288) while in subpopulation AFR AF= 0.0256 (1064/41546). AF 95% confidence interval is 0.0243. There are 16 homozygotes in gnomad4. There are 530 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM48	NM_032120.4 link	c.8C>T	p.Ser3Leu	missense_variant	Exon 1 of 5	ENST00000265732.10	NP_115496.2	Q5RL73-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RBM48	ENST00000265732.10 link	c.8C>T	p.Ser3Leu	missense_variant	Exon 1 of 5	1	NM_032120.4	ENSP00000265732.5	Q5RL73-1
RBM48	ENST00000481551.5 link	c.8C>T	p.Ser3Leu	missense_variant	Exon 1 of 4	1		ENSP00000419242.1	Q5RL73-2
RBM48	ENST00000496410 link	c.-426C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	3		ENSP00000418333.1	C9J787
RBM48	ENST00000496410 link	c.-426C>T		5_prime_UTR_variant	Exon 1 of 3	3		ENSP00000418333.1	C9J787

Frequencies

GnomAD3 genomes

AF:

0.00733

AC:

1115

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0255

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

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:

0.0000294

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00173

AC:

431

AN:

248726

Hom.:

AF XY:

0.00126

AC XY:

170

AN XY:

135148

show subpopulations

Gnomad AFR exome

AF:

0.0251

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000726

AC:

1061

AN:

1461572

Hom.:

Cov.:

AF XY:

0.000593

AC XY:

431

AN XY:

727074

show subpopulations

Gnomad4 AFR exome

AF:

0.0264

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00176

GnomAD4 genome

AF:

0.00736

AC:

1121

AN:

152288

Hom.:

Cov.:

AF XY:

0.00712

AC XY:

530

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0256

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.00836

ESP6500AA

AF:

0.0239

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00209

AC:

252

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 11, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.027

Sift

Benign

0.030

D;D

Sift4G

Benign

0.090

T;T

Polyphen

0.14

B;.

Vest4

0.13

MVP

0.74

MPC

0.19

ClinPred

0.054

GERP RS

2.8

Varity_R

0.11

gMVP

0.61

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over