chr14-61782321-A-C

Position:

• chr14-61782321-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003082.4(SNAPC1):​c.900A>C​(p.Gln300His) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNAPC1 NM_003082.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.132

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054572105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAPC1	NM_003082.4	c.900A>C	p.Gln300His	missense_variant	8/10	ENST00000216294.5	NP_003073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAPC1	ENST00000216294.5	c.900A>C	p.Gln300His	missense_variant	8/10	1	NM_003082.4	ENSP00000216294.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Apr 09, 2024

The c.900A>C (p.Q300H) alteration is located in exon 8 (coding exon 8) of the SNAPC1 gene. This alteration results from a A to C substitution at nucleotide position 900, causing the glutamine (Q) at amino acid position 300 to be replaced by a histidine (H). 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	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.028
Sift	Benign	0.12	T
Sift4G	Benign	0.14	T
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.22		Gain of catalytic residue at Q298 (P = 0.0819);
MVP		0.11
MPC		0.18
ClinPred		0.34	T
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.051
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr14-62249039;