NM_003083.4:c.414C>G

Variant names:

• chr19-7922076-C-G
• rs202107483
• NM_003083.4:c.414C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003083.4(SNAPC2):​c.414C>G​(p.His138Gln) variant causes a missense change involving the alteration of a non-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: 32)
• Consequence: SNAPC2 NM_003083.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49
• Publications: 0 publications found

Genes affected

SNAPC2 (HGNC:11135): (small nuclear RNA activating complex polypeptide 2) This gene encodes a subunit of the snRNA-activating protein complex which is associated with the TATA box-binding protein. The encoded protein is necessary for RNA polymerase II and III dependent small-nuclear RNA gene transcription. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003083.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAPC2	NM_003083.4	MANE Select	c.414C>G	p.His138Gln	missense	Exon 4 of 5	NP_003074.1	Q13487
	SNAPC2	NR_030717.2		n.336C>G		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAPC2	ENST00000221573.11	TSL:1 MANE Select	c.414C>G	p.His138Gln	missense	Exon 4 of 5	ENSP00000221573.5	Q13487
	SNAPC2	ENST00000597584.5	TSL:1	c.-298C>G		5_prime_UTR	Exon 4 of 5	ENSP00000471962.1	M0R1L8
	SNAPC2	ENST00000853925.1		c.414C>G	p.His138Gln	missense	Exon 4 of 5	ENSP00000523984.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.5
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.52		Gain of relative solvent accessibility (P = 0.0289)
MVP		0.65
MPC		0.36
ClinPred		0.99	D
GERP RS		2.7
Varity_R		0.71
gMVP		0.44
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs202107483; hg19: chr19-7986961;