Variant chr6-7590339-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152551.4(SNRNP48):c.82A>G(p.Thr28Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000407 in 1,401,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

SNRNP48
NM_152551.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07352173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNRNP48	NM_152551.4 linkuse as main transcript	c.82A>G	p.Thr28Ala	missense_variant	1/9	ENST00000342415.6	NP_689764.3	Q6IEG0-1
SNRNP48	XM_011514312.4 linkuse as main transcript	c.82A>G	p.Thr28Ala	missense_variant	1/9		XP_011512614.1
SNRNP48	XM_047418238.1 linkuse as main transcript	c.82A>G	p.Thr28Ala	missense_variant	1/5		XP_047274194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNRNP48	ENST00000342415.6 linkuse as main transcript	c.82A>G	p.Thr28Ala	missense_variant	1/9	1	NM_152551.4	ENSP00000339834.4		Q6IEG0-1
SNRNP48	ENST00000634363.1 linkuse as main transcript	n.82A>G		non_coding_transcript_exon_variant	1/8	2		ENSP00000489245.1		A0A0U1RQZ2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000883

AC:

AN:

135838

Hom.:

AF XY:

0.000108

AC XY:

AN XY:

74258

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000631

Gnomad NFE exome

AF:

0.000166

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000392

AC:

AN:

1249650

Hom.:

Cov.:

AF XY:

0.0000392

AC XY:

AN XY:

612384

show subpopulations

Gnomad4 AFR exome

AF:

0.0000371

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:

0.0000223

Gnomad4 NFE exome

AF:

0.0000472

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152044

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000604

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.000116

AC:

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

Dec 02, 2022

The c.82A>G (p.T28A) alteration is located in exon 1 (coding exon 1) of the SNRNP48 gene. This alteration results from a A to G substitution at nucleotide position 82, causing the threonine (T) at amino acid position 28 to be replaced by an alanine (A). 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

Benign

0.096

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.013

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.087

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.59

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.55

REVEL

Benign

0.053

Sift

Benign

0.32

Sift4G

Benign

0.44

Polyphen

0.043

Vest4

0.31

MutPred

0.13

Gain of helix (P = 0.0199);

MVP

0.38

MPC

0.31

ClinPred

0.11

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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