19-7920373-C-A

Variant names:

• chr19-7920373-C-A
• rs1276166083
• NM_003083.4:c.7C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003083.4(SNAPC2):​c.7C>A​(p.Pro3Thr) 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 1,423,716 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P3S) has been classified as Uncertain significance.

• 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: 0.998
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.7C>A	p.Pro3Thr	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.7C>A	p.Pro3Thr	missense	Exon 1 of 5	ENSP00000221573.5	Q13487
	SNAPC2	ENST00000853925.1		c.7C>A	p.Pro3Thr	missense	Exon 1 of 5	ENSP00000523984.1
	SNAPC2	ENST00000971261.1		c.7C>A	p.Pro3Thr	missense	Exon 1 of 4	ENSP00000641320.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1423716 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 708236

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29992

American (AMR) AF: 0.00 AC: 0 AN: 42566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25148

East Asian (EAS) AF: 0.00 AC: 0 AN: 36028

South Asian (SAS) AF: 0.00 AC: 0 AN: 84382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1101100

Other (OTH) AF: 0.00 AC: 0 AN: 59192

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.40		Gain of phosphorylation at P3 (P = 0.0019)
MVP		0.81
MPC		0.063
ClinPred		1.0	D
GERP RS		4.2
PromoterAI		-0.052	Neutral
Varity_R		0.89
gMVP		0.46
Mutation Taster		=76/24	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: rs1276166083; hg19: chr19-7985258;