19-7921474-C-G

Variant names:

• chr19-7921474-C-G
• rs748854268
• ENST00000597584:c.-477C>G

Variant summary

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

The ENST00000597584(SNAPC2):​c.-477C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SNAPC2 ENST00000597584 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

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

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=0.27718124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAPC2	NM_003083.4	c.235C>G	p.Gln79Glu	missense_variant	Exon 2 of 5	ENST00000221573.11	NP_003074.1
SNAPC2	NR_030717.2	n.157C>G		non_coding_transcript_exon_variant	Exon 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAPC2	ENST00000221573.11	c.235C>G	p.Gln79Glu	missense_variant	Exon 2 of 5	1	NM_003083.4	ENSP00000221573.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 250932 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135720

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461568 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727096

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: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.097
Sift	Uncertain	0.019	D
Sift4G	Benign	0.091	T
Polyphen		0.98	D
Vest4		0.41
MutPred		0.20		Loss of MoRF binding (P = 0.0457);
MVP		0.64
MPC		0.33
ClinPred		0.39	T
GERP RS		4.0
Varity_R		0.17
gMVP		0.18

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

Other links and lift over

dbSNP: rs748854268; hg19: chr19-7986359;