15-101284975-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003090.4(SNRPA1):​c.701G>A​(p.Arg234His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,611,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R234C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SNRPA1
NM_003090.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76
Variant links:
Genes affected
SNRPA1 (HGNC:11152): (small nuclear ribonucleoprotein polypeptide A') Enables RNA binding activity. Involved in mRNA splicing, via spliceosome and spermatogenesis. Located in nuclear speck. Part of U2-type catalytic step 2 spliceosome and U2-type precatalytic spliceosome. Implicated in connective tissue disease. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09784514).
BS2
High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNRPA1NM_003090.4 linkc.701G>A p.Arg234His missense_variant Exon 8 of 9 ENST00000254193.11 NP_003081.2 P09661
SNRPA1NR_135506.2 linkn.464G>A non_coding_transcript_exon_variant Exon 5 of 6
SNRPA1NR_135507.2 linkn.417G>A non_coding_transcript_exon_variant Exon 4 of 5
SNRPA1NR_135508.2 linkn.691G>A non_coding_transcript_exon_variant Exon 7 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNRPA1ENST00000254193.11 linkc.701G>A p.Arg234His missense_variant Exon 8 of 9 1 NM_003090.4 ENSP00000254193.6 P09661

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152232
Hom.:
0
Cov.:
33
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251410
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1459656
Hom.:
0
Cov.:
29
AF XY:
0.0000138
AC XY:
10
AN XY:
726234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152232
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 12, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.701G>A (p.R234H) alteration is located in exon 8 (coding exon 8) of the SNRPA1 gene. This alteration results from a G to A substitution at nucleotide position 701, causing the arginine (R) at amino acid position 234 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
Benign
0.10
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.046
T;.;T
Eigen
Benign
-0.12
Eigen_PC
Benign
0.094
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.74
T;T;T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.098
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.85
L;.;.
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-0.64
N;N;N
REVEL
Benign
0.036
Sift
Benign
0.13
T;T;T
Sift4G
Benign
0.24
T;T;T
Polyphen
0.0080
B;.;.
Vest4
0.18
MutPred
0.087
Gain of helix (P = 0.062);.;.;
MVP
0.51
MPC
0.79
ClinPred
0.22
T
GERP RS
5.6
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.041
gMVP
0.28

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.

Other links and lift over

dbSNP: rs753401813; hg19: chr15-101825180; API