chr15-101286969-A-G

Position:

• chr15-101286969-A-G

Variant summary

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

The NM_003090.4(SNRPA1):​c.398T>C​(p.Leu133Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNRPA1 NM_003090.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.79

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNRPA1	NM_003090.4	c.398T>C	p.Leu133Ser	missense_variant	5/9	ENST00000254193.11
SNRPA1	NR_135506.2	n.241T>C		non_coding_transcript_exon_variant	3/6
SNRPA1	NR_135507.2	n.194T>C		non_coding_transcript_exon_variant	2/5
SNRPA1	NR_135508.2	n.468T>C		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNRPA1	ENST00000254193.11	c.398T>C	p.Leu133Ser	missense_variant	5/9	1	NM_003090.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

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

Aug 21, 2023

The c.398T>C (p.L133S) alteration is located in exon 5 (coding exon 5) of the SNRPA1 gene. This alteration results from a T to C substitution at nucleotide position 398, causing the leucine (L) at amino acid position 133 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	0.58
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T;.
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.4	L;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.5	D;D;.
REVEL	Uncertain	0.38
Sift	Benign	0.11	T;T;.
Sift4G	Benign	0.16	T;D;T
Polyphen		0.19	B;.;.
Vest4		0.83
MutPred		0.50		Loss of stability (P = 0.002);.;Loss of stability (P = 0.002);
MVP		0.72
MPC		1.2
ClinPred		0.95	D
GERP RS		5.6
Varity_R		0.30
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-101827174;