Variant 19-49108325-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003089.6(SNRNP70):c.1196A>C(p.Gln399Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SNRNP70
NM_003089.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.900

Variant links:

Genes affected

SNRNP70 (HGNC:11150): (small nuclear ribonucleoprotein U1 subunit 70) Enables U1 snRNA binding activity. Involved in mRNA splicing, via spliceosome and regulation of RNA splicing. Located in nucleoplasm. Part of U1 snRNP and spliceosomal complex. Implicated in disease of mental health and systemic lupus erythematosus. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

SNRNP70 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049409002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNRNP70	NM_003089.6 linkuse as main transcript	c.1196A>C	p.Gln399Pro	missense_variant	10/10	ENST00000598441.6	NP_003080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNRNP70	ENST00000598441.6 linkuse as main transcript	c.1196A>C	p.Gln399Pro	missense_variant	10/10	1	NM_003089.6	ENSP00000472998	P3	P08621-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000448

AC:

AN:

223170

Hom.:

AF XY:

0.00

AC XY:

AN XY:

121100

show subpopulations

Gnomad AFR exome

AF:

0.0000747

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000240

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000826

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

Jun 29, 2022

The c.1196A>C (p.Q399P) alteration is located in exon 10 (coding exon 9) of the SNRNP70 gene. This alteration results from a A to C substitution at nucleotide position 1196, causing the glutamine (Q) at amino acid position 399 to be replaced by a proline (P). 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

0.085

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.60

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.049

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

0.75

D;D;N

PrimateAI

Uncertain

0.69

REVEL

Benign

0.045

Sift4G

Benign

0.23

T;T

Polyphen

0.28

B;B

Vest4

0.27

MutPred

0.28

Loss of MoRF binding (P = 0.082);.;

MVP

0.27

MPC

1.3

ClinPred

0.080

GERP RS

1.3

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.068

gMVP

0.14

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