rs1182655008

Variant names:

• chr19-7920431-C-T
• rs1182655008
• NM_003083.4:c.65C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-7920431-C-T
• chr19-7920431-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003083.4(SNAPC2):​c.65C>T​(p.Ala22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,572,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: SNAPC2 NM_003083.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.205
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045874476).

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.65C>T	p.Ala22Val	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.65C>T	p.Ala22Val	missense	Exon 1 of 5	ENSP00000221573.5	Q13487
	SNAPC2	ENST00000853925.1		c.65C>T	p.Ala22Val	missense	Exon 1 of 5	ENSP00000523984.1
	SNAPC2	ENST00000971261.1		c.65C>T	p.Ala22Val	missense	Exon 1 of 4	ENSP00000641320.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152108 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000165 AC: 3 AN: 181414 AF XY: 0.0000196

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000980

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000253 AC: 36 AN: 1420468 Hom.: 0 Cov.: 32 AF XY: 0.0000283 AC XY: 20 AN XY: 705720

African (AFR) AF: 0.00 AC: 0 AN: 30352

American (AMR) AF: 0.0000713 AC: 3 AN: 42098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25044

East Asian (EAS) AF: 0.00 AC: 0 AN: 36694

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5472

European-Non Finnish (NFE) AF: 0.0000282 AC: 31 AN: 1099980

Other (OTH) AF: 0.0000169 AC: 1 AN: 59024

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152108 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74312

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

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	Benign	0.095
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.28	N
PhyloP100		0.20
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.021
Sift	Benign	1.0	T
Sift4G	Benign	0.22	T
Polyphen		0.37	B
Vest4		0.11
MutPred		0.17		Loss of relative solvent accessibility (P = 0.0676)
MVP		0.47
MPC		0.065
ClinPred		0.046	T
GERP RS		0.69
PromoterAI		0.25	Neutral
Varity_R		0.057
gMVP		0.11
Mutation Taster		=100/0	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: rs1182655008; hg19: chr19-7985316;