19-7920535-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003083.4(SNAPC2):​c.169C>T​(p.Arg57Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000844 in 1,184,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 31)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: SNAPC2 NM_003083.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

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>T	p.Arg57Trp	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>T	p.Arg57Trp	missense	Exon 1 of 5	ENSP00000221573.5	Q13487
	SNAPC2	ENST00000853925.1		c.169C>T	p.Arg57Trp	missense	Exon 1 of 5	ENSP00000523984.1
	SNAPC2	ENST00000971261.1		c.169C>T	p.Arg57Trp	missense	Exon 1 of 4	ENSP00000641320.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.44e-7 AC: 1 AN: 1184358 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 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: 0.00000103 AC: 1 AN: 970508

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.36	N
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.89	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.061
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.29
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.65		Loss of disorder (P = 0.0091)
MVP		0.75
MPC		0.37
ClinPred		0.99	D
GERP RS		1.8
PromoterAI		-0.061	Neutral
Varity_R		0.43
gMVP		0.68
Mutation Taster		=89/11	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;