chr19-7920535-C-G

Variant names:

• chr19-7920535-C-G
• rs767538607
• NM_003083.4:c.169C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003083.4(SNAPC2):​c.169C>G​(p.Arg57Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000903 in 1,329,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R57P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: SNAPC2 NM_003083.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0610
• 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]

ENSG00000260500 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4089981).

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.169C>G	p.Arg57Gly	missense	Exon 1 of 5	NP_003074.1	Q13487

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAPC2	ENST00000221573.11	TSL:1 MANE Select	c.169C>G	p.Arg57Gly	missense	Exon 1 of 5	ENSP00000221573.5	Q13487
	SNAPC2	ENST00000853925.1		c.169C>G	p.Arg57Gly	missense	Exon 1 of 5	ENSP00000523984.1
	SNAPC2	ENST00000971261.1		c.169C>G	p.Arg57Gly	missense	Exon 1 of 4	ENSP00000641320.1

Frequencies

GnomAD3 genomes AF: 0.0000207 AC: 3 AN: 145144 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000510

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000260 AC: 1 AN: 38520 AF XY: 0.0000439

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000700

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000760 AC: 9 AN: 1184358 Hom.: 0 Cov.: 28 AF XY: 0.00000692 AC XY: 4 AN XY: 577664

African (AFR) AF: 0.00 AC: 0 AN: 22520

American (AMR) AF: 0.00 AC: 0 AN: 16664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16462

East Asian (EAS) AF: 0.00 AC: 0 AN: 21168

South Asian (SAS) AF: 0.00 AC: 0 AN: 64662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3290

European-Non Finnish (NFE) AF: 0.00000927 AC: 9 AN: 970508

Other (OTH) AF: 0.00 AC: 0 AN: 47126

GnomAD4 genome AF: 0.0000207 AC: 3 AN: 145144 Hom.: 0 Cov.: 31 AF XY: 0.0000425 AC XY: 3 AN XY: 70508

African (AFR) AF: 0.0000510 AC: 2 AN: 39222

American (AMR) AF: 0.00 AC: 0 AN: 14648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3374

East Asian (EAS) AF: 0.00 AC: 0 AN: 4790

South Asian (SAS) AF: 0.00 AC: 0 AN: 4408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66228

Other (OTH) AF: 0.00 AC: 0 AN: 2012

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000822 AC: 4

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	Pathogenic	0.82
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.85	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.061
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.23
Sift	Uncertain	0.013	D
Sift4G	Benign	0.16	T
Polyphen		0.0070	B
Vest4		0.43
MutPred		0.54		Loss of methylation at R57 (P = 0.0508)
MVP		0.67
MPC		0.085
ClinPred		0.28	T
GERP RS		1.8
PromoterAI		-0.065	Neutral
Varity_R		0.28
gMVP		0.69
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs767538607; hg19: chr19-7985420;