chr19-7920538-A-G

Variant names:

• chr19-7920538-A-G
• NM_003083.4:c.172A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003083.4(SNAPC2):​c.172A>G​(p.Ser58Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000633 in 1,263,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: SNAPC2 NM_003083.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.305
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26383638).

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.172A>G	p.Ser58Gly	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.172A>G	p.Ser58Gly	missense	Exon 1 of 5	ENSP00000221573.5	Q13487
	SNAPC2	ENST00000853925.1		c.172A>G	p.Ser58Gly	missense	Exon 1 of 5	ENSP00000523984.1
	SNAPC2	ENST00000971261.1		c.172A>G	p.Ser58Gly	missense	Exon 1 of 4	ENSP00000641320.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000633 AC: 8 AN: 1263978 Hom.: 0 Cov.: 27 AF XY: 0.00000647 AC XY: 4 AN XY: 618642

African (AFR) AF: 0.00 AC: 0 AN: 24588

American (AMR) AF: 0.00 AC: 0 AN: 19414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19470

East Asian (EAS) AF: 0.0000700 AC: 2 AN: 28580

South Asian (SAS) AF: 0.00 AC: 0 AN: 65156

European-Finnish (FIN) AF: 0.0000329 AC: 1 AN: 30436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3682

European-Non Finnish (NFE) AF: 0.00000392 AC: 4 AN: 1020514

Other (OTH) AF: 0.0000192 AC: 1 AN: 52138

GnomAD4 genome Cov.: 30

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	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.71	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.30
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.12
Sift	Benign	0.056	T
Sift4G	Benign	0.23	T
Polyphen		0.029	B
Vest4		0.43
MutPred		0.32		Loss of phosphorylation at S58 (P = 0.005)
MVP		0.59
MPC		0.068
ClinPred		0.26	T
GERP RS		4.1
PromoterAI		-0.033	Neutral
Varity_R		0.22
gMVP		0.42
Mutation Taster		=90/10	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

hg19: chr19-7985423;