19-7920525-G-C

Variant names:

• chr19-7920525-G-C
• rs953281812
• NM_003083.4:c.159G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003083.4(SNAPC2):​c.159G>C​(p.Glu53Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNAPC2 NM_003083.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.848

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14338171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAPC2	NM_003083.4	c.159G>C	p.Glu53Asp	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.159G>C	p.Glu53Asp	missense_variant	Exon 1 of 5	1	NM_003083.4	ENSP00000221573.5
SNAPC2	ENST00000595637.1	c.138G>C	p.Glu46Asp	missense_variant	Exon 1 of 4	2		ENSP00000469475.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1296844 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 636164

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.159G>C (p.E53D) alteration is located in exon 1 (coding exon 1) of the SNAPC2 gene. This alteration results from a G to C substitution at nucleotide position 159, causing the glutamic acid (E) at amino acid position 53 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.76
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.035
Sift	Benign	0.53	T
Sift4G	Benign	0.43	T
Polyphen		0.46	P
Vest4		0.25
MutPred		0.14		Gain of MoRF binding (P = 0.1268);
MVP		0.56
MPC		0.12
ClinPred		0.22	T
GERP RS		3.1
Varity_R		0.085
gMVP		0.24

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: rs953281812; hg19: chr19-7985410;