9-15423175-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001039697.2(SNAPC3):c.296A>C(p.Glu99Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000702 in 1,425,264 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: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SNAPC3 NM_001039697.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.93

Genes affected

SNAPC3 (HGNC:11136): (small nuclear RNA activating complex polypeptide 3) Predicted to enable RNA polymerase III type 3 promoter sequence-specific DNA binding activity and bent DNA binding activity. Predicted to contribute to RNA polymerase II cis-regulatory region sequence-specific DNA binding activity and core promoter sequence-specific DNA binding activity. Predicted to be involved in snRNA transcription by RNA polymerase II and snRNA transcription by RNA polymerase III. Located in nuclear body and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34067476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAPC3	NM_001039697.2	c.296A>C	p.Glu99Ala	missense_variant	1/9	ENST00000380821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAPC3	ENST00000380821.8	c.296A>C	p.Glu99Ala	missense_variant	1/9	1	NM_001039697.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1425264 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 709250

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: 9.07e-7

Gnomad4 OTH exome AF: 0.00

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

Apr 07, 2023

The c.296A>C (p.E99A) alteration is located in exon 1 (coding exon 1) of the SNAPC3 gene. This alteration results from a A to C substitution at nucleotide position 296, causing the glutamic acid (E) at amino acid position 99 to be replaced by an alanine (A). 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	0.22
BayesDel_addAF	Benign	0.0096	T
BayesDel_noAF	Benign	-0.22
Cadd	Pathogenic	27
Dann	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.76	D
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.5	M;M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.2	D;.;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.026	D;.;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.97	D;D;.
Vest4		0.56
MutPred		0.47		Loss of disorder (P = 0.1077);Loss of disorder (P = 0.1077);Loss of disorder (P = 0.1077);
MVP		0.71
MPC		0.088
ClinPred		0.99	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.60

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: chr9-15423173;