rs796052169

Positions:

• chr15-66494510-T-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The ENST00000316634.6(SNAPC5):​c.223A>G​(p.Thr75Ala) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNAPC5 ENST00000316634.6 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0430

Genes affected

SNAPC5 (HGNC:15484): (small nuclear RNA activating complex polypeptide 5) This gene encodes a subunit of the small nuclear RNA (snRNA)-activating protein complex that plays a role in the transcription of snRNA genes. This complex binds to the promoters of snRNA genes transcribed by either RNA polymerase II or III and recruits other regulatory factors to activate snRNA gene transcription. The encoded protein may play a role in stabilizing this complex. A pseudogene of this gene has been identified on chromosome 6. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061212122).
• BP6: Variant 15-66494510-T-C is Benign according to our data. Variant chr15-66494510-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 207880.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAPC5	NM_001329615.2	c.223A>G	p.Thr75Ala	missense_variant	3/3	ENST00000316634.6	NP_001316544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAPC5	ENST00000316634.6	c.223A>G	p.Thr75Ala	missense_variant	3/3	1	NM_001329615.2	ENSP00000319597	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome Benign:1

Likely benign, no assertion criteria provided

research

Medical Research Institute, Tokyo Medical and Dental University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.7
DANN	Benign	0.70
DEOGEN2	Benign	0.038	T;T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.45	.;.;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.061	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.93	N;N;N;N
REVEL	Benign	0.087
Sift	Benign	0.50	T;T;T;T
Sift4G	Benign	0.67	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.024
MutPred		0.13		Loss of glycosylation at T75 (P = 0.0537);Loss of glycosylation at T75 (P = 0.0537);Loss of glycosylation at T75 (P = 0.0537);.;
MVP		0.061
MPC		0.024
ClinPred		0.27	T
GERP RS		0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.026

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

Publications

LitVar

Other links and lift over

dbSNP: rs796052169; hg19: chr15-66786848;