14-61766950-C-G

Position:

• chr14-61766950-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003082.4(SNAPC1):​c.203C>G​(p.Pro68Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNAPC1 NM_003082.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.83

Genes affected

SNAPC1 (HGNC:11134): (small nuclear RNA activating complex polypeptide 1) Predicted to enable sequence-specific DNA binding activity. Predicted to be involved in snRNA transcription by RNA polymerase II and snRNA transcription by RNA polymerase III. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258964 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.876

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAPC1	NM_003082.4	c.203C>G	p.Pro68Arg	missense_variant	2/10	ENST00000216294.5	NP_003073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAPC1	ENST00000216294.5	c.203C>G	p.Pro68Arg	missense_variant	2/10	1	NM_003082.4	ENSP00000216294.4
ENSG00000258964	ENST00000555937.1	n.223C>G		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 08, 2022

The c.203C>G (p.P68R) alteration is located in exon 2 (coding exon 2) of the SNAPC1 gene. This alteration results from a C to G substitution at nucleotide position 203, causing the proline (P) at amino acid position 68 to be replaced by an arginine (R). 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	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.056	D
MutationAssessor	Uncertain	2.9	M
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Pathogenic	0.73
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.71		Gain of MoRF binding (P = 0.0022);
MVP		0.52
MPC		0.29
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.76
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-62233668;