Variant chr19-45687564-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001384647.1(SNRPD2):c.346G>A(p.Ala116Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SNRPD2
NM_001384647.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.89

Variant links:

Genes affected

SNRPD2 (HGNC:11159): (small nuclear ribonucleoprotein D2 polypeptide) The protein encoded by this gene belongs to the small nuclear ribonucleoprotein core protein family. It is required for pre-mRNA splicing and small nuclear ribonucleoprotein biogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

SNRPD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11857405).

BS2

High AC in GnomAdExome4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNRPD2	NM_001384647.1 linkuse as main transcript	c.346G>A	p.Ala116Thr	missense_variant	3/3	ENST00000342669.8	NP_001371576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNRPD2	ENST00000342669.8 linkuse as main transcript	c.346G>A	p.Ala116Thr	missense_variant	3/3	1	NM_001384647.1	ENSP00000342374	P1	P62316-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251050

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135654

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461666

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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

Mar 01, 2023

The c.346G>A (p.A116T) alteration is located in exon 3 (coding exon 3) of the SNRPD2 gene. This alteration results from a G to A substitution at nucleotide position 346, causing the alanine (A) at amino acid position 116 to be replaced by a threonine (T). 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

0.074

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;T;.;.;.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

0.071

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.85

.;T;.;.;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.12

T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.79

N;.;.;.;.;N

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.62

N;.;.;.;N;.

REVEL

Benign

0.081

Sift

Benign

0.25

T;.;.;.;T;.

Sift4G

Benign

0.15

.;T;T;T;T;.

Polyphen

0.0020

B;.;.;.;.;B

Vest4

0.14

MutPred

0.21

Gain of sheet (P = 0.0266);.;.;.;.;Gain of sheet (P = 0.0266);

MVP

0.24

MPC

1.4

ClinPred

0.20

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.40

gMVP

0.90

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