chr19-7920469-C-T

Variant names:

• chr19-7920469-C-T
• rs769557821
• NM_003083.4:c.103C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003083.4(SNAPC2):​c.103C>T​(p.Leu35Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000209 in 1,534,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.000022 (0 hom.)
• Consequence: SNAPC2 NM_003083.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3633923).

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.103C>T	p.Leu35Phe	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.103C>T	p.Leu35Phe	missense	Exon 1 of 5	ENSP00000221573.5	Q13487
	SNAPC2	ENST00000853925.1		c.103C>T	p.Leu35Phe	missense	Exon 1 of 5	ENSP00000523984.1
	SNAPC2	ENST00000971261.1		c.103C>T	p.Leu35Phe	missense	Exon 1 of 4	ENSP00000641320.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152020 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000768 AC: 1 AN: 130178 AF XY: 0.0000137

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000224 AC: 31 AN: 1382262 Hom.: 0 Cov.: 32 AF XY: 0.0000249 AC XY: 17 AN XY: 683364

African (AFR) AF: 0.00 AC: 0 AN: 29032

American (AMR) AF: 0.00 AC: 0 AN: 36620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24462

East Asian (EAS) AF: 0.00 AC: 0 AN: 34064

South Asian (SAS) AF: 0.00 AC: 0 AN: 79532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4834

European-Non Finnish (NFE) AF: 0.0000278 AC: 30 AN: 1080878

Other (OTH) AF: 0.0000173 AC: 1 AN: 57658

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152020 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74232

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

African (AFR) AF: 0.0000242 AC: 1 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

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: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000949 AC: 1

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	0.25
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.080
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.6
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.11
Sift	Benign	0.22	T
Sift4G	Benign	0.067	T
Polyphen		1.0	D
Vest4		0.41
MutPred		0.27		Loss of MoRF binding (P = 0.1368)
MVP		0.62
MPC		0.38
ClinPred		0.91	D
GERP RS		3.1
PromoterAI		0.029	Neutral
Varity_R		0.087
gMVP		0.31
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

dbSNP: rs769557821; hg19: chr19-7985354;