chr9-15453061-A-G

Position:

• chr9-15453061-A-G

Variant summary

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

The NM_001039697.2(SNAPC3):​c.836A>G​(p.Glu279Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SNAPC3 NM_001039697.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

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]

SNAPC3 (HGNC:):

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	Protein	UniProt
SNAPC3	NM_001039697.2	c.836A>G	p.Glu279Gly	missense_variant	7/9	ENST00000380821.8	NP_001034786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAPC3	ENST00000380821.8	c.836A>G	p.Glu279Gly	missense_variant	7/9	1	NM_001039697.2	ENSP00000370200.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

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

May 02, 2024

The c.836A>G (p.E279G) alteration is located in exon 7 (coding exon 7) of the SNAPC3 gene. This alteration results from a A to G substitution at nucleotide position 836, causing the glutamic acid (E) at amino acid position 279 to be replaced by a glycine (G). 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	0.16
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T;.;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	.;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.1	M;M;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.6	D;.;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.018	D;.;D;D
Sift4G	Uncertain	0.047	D;D;D;T
Polyphen		0.99	D;D;.;.
Vest4		0.51
MutPred		0.39		Loss of stability (P = 0.0605);Loss of stability (P = 0.0605);.;.;
MVP		0.59
MPC		0.17
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.41
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.30		Position offset: -20

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: chr9-15453059;