Variant 6-7593749-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong

The NM_152551.4(SNRNP48):c.172T>C(p.Cys58Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000281 in 1,425,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

SNRNP48
NM_152551.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.14

Variant links:

Genes affected

SNRNP48 (HGNC:21368): (small nuclear ribonucleoprotein U11/U12 subunit 48) Predicted to enable metal ion binding activity. Predicted to be involved in RNA splicing. Located in cytosol and nucleoplasm. Part of U12-type spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

SNRNP48 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity SNR48_HUMAN

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.95

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SNRNP48	NM_152551.4 linkuse as main transcript	c.172T>C	p.Cys58Arg	missense_variant	2/9	ENST00000342415.6
SNRNP48	XM_011514312.4 linkuse as main transcript	c.109T>C	p.Cys37Arg	missense_variant	2/9
SNRNP48	XM_047418238.1 linkuse as main transcript	c.172T>C	p.Cys58Arg	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNRNP48	ENST00000342415.6 linkuse as main transcript	c.172T>C	p.Cys58Arg	missense_variant	2/9	1	NM_152551.4	P1	Q6IEG0-1
SNRNP48	ENST00000634363.1 linkuse as main transcript	c.172T>C	p.Cys58Arg	missense_variant, NMD_transcript_variant	2/8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000281

AC:

AN:

1425142

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

707220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000314

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000274

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.172T>C (p.C58R) alteration is located in exon 2 (coding exon 2) of the SNRNP48 gene. This alteration results from a T to C substitution at nucleotide position 172, causing the cysteine (C) at amino acid position 58 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.56

BayesDel_noAF

Pathogenic

0.56

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.92

MetaRNN

Pathogenic

0.95

MetaSVM

Uncertain

0.78

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-11

REVEL

Pathogenic

0.93

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.97

MutPred

0.71

Loss of catalytic residue at S62 (P = 0.0155);

MVP

0.92

MPC

1.4

ClinPred

1.0

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.97

gMVP

0.84

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