rs758691448

Variant names:

• chr19-7920428-C-G
• NM_003083.4:c.62C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-7920428-C-G
• chr19-7920428-C-T

Variant summary

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

The NM_003083.4(SNAPC2):​c.62C>G​(p.Pro21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SNAPC2 NM_003083.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459

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=0.3367318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAPC2	NM_003083.4	c.62C>G	p.Pro21Arg	missense_variant	Exon 1 of 5	ENST00000221573.11	NP_003074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAPC2	ENST00000221573.11	c.62C>G	p.Pro21Arg	missense_variant	Exon 1 of 5	1	NM_003083.4	ENSP00000221573.5
SNAPC2	ENST00000595637.1	c.41C>G	p.Pro14Arg	missense_variant	Exon 1 of 4	2		ENSP00000469475.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424336 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 707896

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: 9.08e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.073
Sift	Benign	0.064	T
Sift4G	Uncertain	0.011	D
Polyphen		0.96	D
Vest4		0.34
MutPred		0.33		Gain of solvent accessibility (P = 0.0246);
MVP		0.78
MPC		0.13
ClinPred		0.82	D
GERP RS		0.48
Varity_R		0.15
gMVP		0.13

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: chr19-7985313;