19-7920535-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAPC2	NM_003083.4	c.169C>T	p.Arg57Trp	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.169C>T	p.Arg57Trp	missense_variant	Exon 1 of 5	1	NM_003083.4	ENSP00000221573.5
SNAPC2	ENST00000595637.1	c.148C>T	p.Arg50Trp	missense_variant	Exon 1 of 4	2		ENSP00000469475.1

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

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: 0.00000103

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	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
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
Varity_R		0.43
gMVP		0.68

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: chr19-7985420;