chr2-69895097-G-A

Position:

• chr2-69895097-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006857.3(SNRNP27):​c.38G>A​(p.Arg13His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SNRNP27 NM_006857.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04

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 (HGNC:):

ACMG classification

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=0.13391969).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNRNP27	NM_006857.3	c.38G>A	p.Arg13His	missense_variant	2/6	ENST00000244227.8	NP_006848.1
SNRNP27	NR_037862.2	n.67G>A		non_coding_transcript_exon_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNRNP27	ENST00000244227.8	c.38G>A	p.Arg13His	missense_variant	2/6	1	NM_006857.3	ENSP00000244227.3
SNRNP27	ENST00000409116.5	c.38G>A	p.Arg13His	missense_variant	2/5	5		ENSP00000386608.1
SNRNP27	ENST00000450162.6	n.38G>A		non_coding_transcript_exon_variant	2/7	2		ENSP00000395144.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460732 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726666

Gnomad4 AFR exome AF: 0.00

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 31, 2024

The c.38G>A (p.R13H) alteration is located in exon 2 (coding exon 2) of the SNRNP27 gene. This alteration results from a G to A substitution at nucleotide position 38, causing the arginine (R) at amino acid position 13 to be replaced by a histidine (H). 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	0.87
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.085	T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.062
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.76	.;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.15
Sift	Benign	0.079	T;T
Sift4G	Uncertain	0.012	D;D
Polyphen		0.0010	B;B
Vest4		0.24
MutPred		0.50		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.44
MPC		1.5
ClinPred		0.99	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.19
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs1676576227; hg19: chr2-70122229; COSMIC: COSV99731969; COSMIC: COSV99731969;