Variant 6-7594157-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152551.4(SNRNP48):c.329T>C(p.Leu110Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000855 in 1,169,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.6e-7 ( 0 hom. )

Consequence

SNRNP48
NM_152551.4 missense, splice_region

Scores

Splicing: ADA: 0.5740

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.759

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SNRNP48	NM_152551.4 linkuse as main transcript	c.329T>C	p.Leu110Ser	missense_variant, splice_region_variant	3/9	ENST00000342415.6	NP_689764.3
SNRNP48	XM_011514312.4 linkuse as main transcript	c.266T>C	p.Leu89Ser	missense_variant, splice_region_variant	3/9		XP_011512614.1
SNRNP48	XM_047418238.1 linkuse as main transcript	c.329T>C	p.Leu110Ser	missense_variant, splice_region_variant	3/5		XP_047274194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNRNP48	ENST00000342415.6 linkuse as main transcript	c.329T>C	p.Leu110Ser	missense_variant, splice_region_variant	3/9	1	NM_152551.4	ENSP00000339834	P1	Q6IEG0-1
SNRNP48	ENST00000634363.1 linkuse as main transcript	c.329T>C	p.Leu110Ser	missense_variant, splice_region_variant, NMD_transcript_variant	3/8	2		ENSP00000489245

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.55e-7

AC:

AN:

1169088

Hom.:

Cov.:

AF XY:

0.00000171

AC XY:

AN XY:

585676

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000112

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 11, 2023

The c.329T>C (p.L110S) alteration is located in exon 3 (coding exon 3) of the SNRNP48 gene. This alteration results from a T to C substitution at nucleotide position 329, causing the leucine (L) at amino acid position 110 to be replaced by a serine (S). 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

0.81

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.46

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.26

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

0.99

Vest4

0.79

MutPred

0.57

Loss of stability (P = 0.0016);

MVP

0.61

MPC

1.1

ClinPred

0.98

GERP RS

5.1

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.45

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.57

dbscSNV1_RF

Benign

0.65

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over