Genetic Variant SNRPD3:p.Gly25Ser (chr22-24557747-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2

The NM_004175.5(SNRPD3):c.73G>A(p.Gly25Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,776 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: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SNRPD3
NM_004175.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.04

Variant links:

Genes affected

SNRPD3 (HGNC:11160): (small nuclear ribonucleoprotein D3 polypeptide) This gene encodes a core component of the spliceosome, which is a nuclear ribonucleoprotein complex that functions in pre-mRNA splicing. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

SNRPD3 links:

ENSG00000286070 (HGNC:):

ENSG00000286070 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.96

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNRPD3	NM_004175.5 link	c.73G>A	p.Gly25Ser	missense_variant	Exon 2 of 4	ENST00000215829.8	NP_004166.1	P62318-1
SNRPD3	NM_001278656.2 link	c.73G>A	p.Gly25Ser	missense_variant	Exon 2 of 4		NP_001265585.1	P62318-1
SNRPD3	NR_103819.1 link	n.513G>A		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNRPD3	ENST00000215829.8 link	c.73G>A	p.Gly25Ser	missense_variant	Exon 2 of 4	1	NM_004175.5	ENSP00000215829.3		P62318-1
ENSG00000286070	ENST00000652248.1 link	n.73G>A		non_coding_transcript_exon_variant	Exon 2 of 20			ENSP00000499210.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249212

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000296

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1459776

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.73G>A (p.G25S) alteration is located in exon 2 (coding exon 1) of the SNRPD3 gene. This alteration results from a G to A substitution at nucleotide position 73, causing the glycine (G) at amino acid position 25 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

0.97

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.87

D;.

Eigen

Pathogenic

0.76

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

.;D

M_CAP

Benign

0.039

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Uncertain

-0.017

MutationAssessor

Pathogenic

3.2

M;M

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-5.9

D;D

REVEL

Uncertain

0.55

Sift

Benign

0.036

D;D

Sift4G

Uncertain

0.028

D;D

Polyphen

1.0

D;.

Vest4

0.81

MutPred

0.91

Loss of catalytic residue at T24 (P = 0.188);Loss of catalytic residue at T24 (P = 0.188);

MVP

0.80

MPC

2.8

ClinPred

0.98

GERP RS

4.7

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.84

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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