14-61762498-C-A

Variant names:

• chr14-61762498-C-A
• rs764113543
• NM_003082.4:c.38C>A

Variant summary

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

The NM_003082.4(SNAPC1):​c.38C>A​(p.Ala13Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000229 in 1,309,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A13V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: SNAPC1 NM_003082.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 2 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: 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=0.0977557).

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.38C>A	p.Ala13Glu	missense	Exon 1 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.38C>A	p.Ala13Glu	missense	Exon 1 of 10	ENSP00000216294.4	Q16533
	SNAPC1	ENST00000923634.1		c.38C>A	p.Ala13Glu	missense	Exon 1 of 11	ENSP00000593693.1
	SNAPC1	ENST00000923637.1		c.38C>A	p.Ala13Glu	missense	Exon 1 of 11	ENSP00000593696.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00000416 AC: 1 AN: 240132 AF XY: 0.00000768

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: 0.00000909

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000229 AC: 3 AN: 1309140 Hom.: 0 Cov.: 33 AF XY: 0.00000155 AC XY: 1 AN XY: 645126

African (AFR) AF: 0.00 AC: 0 AN: 29080

American (AMR) AF: 0.00 AC: 0 AN: 36450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21754

East Asian (EAS) AF: 0.00 AC: 0 AN: 31302

South Asian (SAS) AF: 0.00 AC: 0 AN: 63192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4914

European-Non Finnish (NFE) AF: 0.00000292 AC: 3 AN: 1025746

Other (OTH) AF: 0.00 AC: 0 AN: 51556

GnomAD4 genome Cov.: 29

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.88
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.040	N
PhyloP100		0.049
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.021
Sift	Benign	0.61	T
Sift4G	Benign	0.61	T
Polyphen		0.0020	B
Vest4		0.17
MutPred		0.43		Gain of disorder (P = 0.0063)
MVP		0.055
MPC		0.050
ClinPred		0.071	T
GERP RS		1.2
PromoterAI		0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.48
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs764113543; hg19: chr14-62229216;