NM_003082.4:c.157A>C

Variant names:

• chr14-61766904-A-C
• NM_003082.4:c.157A>C

Variant summary

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

The NM_003082.4(SNAPC1):​c.157A>C​(p.Met53Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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: 1.27
• Publications: 0 publications found

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

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=0.05428639).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003082.4. 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
	SNAPC1	NM_003082.4	MANE Select	c.157A>C	p.Met53Leu	missense	Exon 2 of 10	NP_003073.1	Q16533

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAPC1	ENST00000216294.5	TSL:1 MANE Select	c.157A>C	p.Met53Leu	missense	Exon 2 of 10	ENSP00000216294.4	Q16533
	SNAPC1	ENST00000923634.1		c.157A>C	p.Met53Leu	missense	Exon 2 of 11	ENSP00000593693.1
	SNAPC1	ENST00000923637.1		c.157A>C	p.Met53Leu	missense	Exon 2 of 11	ENSP00000593696.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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	0.10
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.88
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.3
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.017
Sift	Benign	0.24	T
Sift4G	Benign	0.31	T
Polyphen		0.0050	B
Vest4		0.14
MutPred		0.26		Loss of methylation at K56 (P = 0.0708)
MVP		0.095
MPC		0.042
ClinPred		0.17	T
GERP RS		3.3
Varity_R		0.052
gMVP		0.30
Mutation Taster		=93/7	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: chr14-62233622;