chr2-69896526-G-C

Position:

chr2-69896526-G-C

Variant summary

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

The NM_006857.3(SNRNP27):c.246G>C(p.Lys82Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,607,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

SNRNP27
NM_006857.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58

Variant links:

Genes affected

SNRNP27 (HGNC:30240): (small nuclear ribonucleoprotein U4/U6.U5 subunit 27) This gene encodes a serine/arginine-rich (SR) protein. SR proteins play important roles in pre-mRNA splicing by facilitating the recognition and selection of splice sites. The encoded protein associates with the 25S U4/U6.U5 tri-snRNP, a major component of the U2-type spiceosome. The expression of this gene may be altered in cells infected with the human T-cell lymphotropic virus type 1 (HTLV-1) retrovirus. A pseudogene of this gene is located on the long arm of chromosome 5. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Feb 2011]

SNRNP27 links:

SNRNP27 (HGNC:):

SNRNP27 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=0.16322517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNRNP27	NM_006857.3 linkuse as main transcript	c.246G>C	p.Lys82Asn	missense_variant	3/6	ENST00000244227.8	NP_006848.1	Q8WVK2A8K513
SNRNP27	NR_037862.2 linkuse as main transcript	n.275G>C		non_coding_transcript_exon_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SNRNP27	ENST00000244227.8 linkuse as main transcript	c.246G>C	p.Lys82Asn	missense_variant	3/6	1	NM_006857.3	ENSP00000244227.3	Q8WVK2
SNRNP27	ENST00000409116.5 linkuse as main transcript	c.246G>C	p.Lys82Asn	missense_variant	3/5	5		ENSP00000386608.1	B8ZZ98
SNRNP27	ENST00000450162.6 linkuse as main transcript	n.246G>C		non_coding_transcript_exon_variant	3/7	2		ENSP00000395144.2	Q8WVK2
SNRNP27	ENST00000488986.1 linkuse as main transcript	n.7G>C		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.000478

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

244906

Hom.:

AF XY:

0.0000375

AC XY:

AN XY:

133214

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:

0.00

Gnomad NFE exome

AF:

0.0000724

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000175

AC:

255

AN:

1454818

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

118

AN XY:

724282

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000196

Gnomad4 NFE exome

AF:

0.000220

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0000481

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:

0.000473

Alfa

AF:

0.0000850

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Oct 25, 2022

The c.246G>C (p.K82N) alteration is located in exon 3 (coding exon 3) of the SNRNP27 gene. This alteration results from a G to C substitution at nucleotide position 246, causing the lysine (K) at amino acid position 82 to be replaced by an asparagine (N). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.043

T;T

Eigen

Benign

0.087

Eigen_PC

Benign

0.048

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.75

.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.089

Sift

Benign

0.33

T;D

Sift4G

Benign

0.45

T;T

Polyphen

0.81

P;D

Vest4

0.33

MutPred

0.36

Loss of methylation at K82 (P = 0.003);Loss of methylation at K82 (P = 0.003);

MVP

0.35

MPC

1.4

ClinPred

0.21

GERP RS

0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.41

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