16-56589-C-T

Variant names:

• chr16-56589-C-T
• rs146101628
• NM_024571.4:c.290C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024571.4(SNRNP25):​c.290C>T​(p.Thr97Met) variant causes a missense change. The variant allele was found at a frequency of 0.000293 in 1,614,030 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: 𝑓 0.00041 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: SNRNP25 NM_024571.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.39

Genes affected

SNRNP25 (HGNC:14161): (small nuclear ribonucleoprotein U11/U12 subunit 25) Two types of spliceosomes catalyze splicing of pre-mRNAs. The major U2-type spliceosome is found in all eukaryotes and removes U2-type introns, which represent more than 99% of pre-mRNA introns. The minor U12-type spliceosome is found in some eukaryotes and removes U12-type introns, which are rare and have distinct splice consensus signals. The U12-type spliceosome consists of several small nuclear RNAs and associated proteins. This gene encodes a 25K protein that is a component of the U12-type spliceosome. [provided by RefSeq, Apr 2010]

ACMG classification

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=0.026893497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNRNP25	NM_024571.4	c.290C>T	p.Thr97Met	missense_variant	Exon 4 of 5	ENST00000293861.8	NP_078847.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNRNP25	ENST00000293861.8	c.290C>T	p.Thr97Met	missense_variant	Exon 4 of 5	1	NM_024571.4	ENSP00000293861.3

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 62 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000406 AC: 102 AN: 251378 Hom.: 0 AF XY: 0.000361 AC XY: 49 AN XY: 135896

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00236

Gnomad NFE exome AF: 0.000369

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000281 AC: 411 AN: 1461684 Hom.: 0 Cov.: 31 AF XY: 0.000294 AC XY: 214 AN XY: 727122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00193

Gnomad4 NFE exome AF: 0.000260

Gnomad4 OTH exome AF: 0.000149

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152346 Hom.: 0 Cov.: 33 AF XY: 0.000470 AC XY: 35 AN XY: 74504

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000422 Hom.: 0

Bravo AF: 0.000193

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000288 AC: 35

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 29, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.317C>T (p.T106M) alteration is located in exon 4 (coding exon 4) of the SNRNP25 gene. This alteration results from a C to T substitution at nucleotide position 317, causing the threonine (T) at amino acid position 106 to be replaced by a methionine (M). 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	0.072
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T;T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.027	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;L;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.060	T;T;T
Sift4G	Benign	0.064	T;T;T
Polyphen		0.99	.;D;.
Vest4		0.48
MVP		0.48
MPC		0.26
ClinPred		0.062	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.073
gMVP		0.38

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

Other links and lift over

dbSNP: rs146101628; hg19: chr16-106589; COSMIC: COSV51955916; COSMIC: COSV51955916;