Variant chr2-69897443-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006857.3(SNRNP27):c.335T>C(p.Phe112Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,612,530 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: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SNRNP27
NM_006857.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.05

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.886

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNRNP27	NM_006857.3 linkuse as main transcript	c.335T>C	p.Phe112Ser	missense_variant	4/6	ENST00000244227.8	NP_006848.1	Q8WVK2A8K513
SNRNP27	NR_037862.2 linkuse as main transcript	n.364T>C		non_coding_transcript_exon_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SNRNP27	ENST00000244227.8 linkuse as main transcript	c.335T>C	p.Phe112Ser	missense_variant	4/6	1	NM_006857.3	ENSP00000244227.3	Q8WVK2
SNRNP27	ENST00000409116.5 linkuse as main transcript	c.335T>C	p.Phe112Ser	missense_variant	4/5	5		ENSP00000386608.1	B8ZZ98
SNRNP27	ENST00000450162.6 linkuse as main transcript	n.335T>C		non_coding_transcript_exon_variant	4/7	2		ENSP00000395144.2	Q8WVK2
SNRNP27	ENST00000488986.1 linkuse as main transcript	n.96T>C		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460350

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726592

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000756

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 30, 2024

The c.335T>C (p.F112S) alteration is located in exon 4 (coding exon 4) of the SNRNP27 gene. This alteration results from a T to C substitution at nucleotide position 335, causing the phenylalanine (F) at amino acid position 112 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

1.0

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

T;T

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

.;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.89

D;D

MetaSVM

Uncertain

-0.0022

MutationAssessor

Pathogenic

3.2

M;.

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-8.0

D;D

REVEL

Pathogenic

0.66

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;T

Polyphen

0.96

P;D

Vest4

0.95

MutPred

0.71

Gain of relative solvent accessibility (P = 0.0098);Gain of relative solvent accessibility (P = 0.0098);

MVP

0.83

MPC

3.3

ClinPred

1.0

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.99

gMVP

0.91

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