rs796052169

Variant names:

• chr15-66494510-T-C
• rs796052169
• NM_001329615.2:c.223A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_001329615.2(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. 15/20 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 NM_001329615.2 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0430
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -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 VariationId is 207880.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329615.2. 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
	SNAPC5	NM_001329615.2	MANE Select	c.223A>G	p.Thr75Ala	missense	Exon 3 of 3	NP_001316544.1	O75971-1
	SNAPC5	NM_006049.4		c.223A>G	p.Thr75Ala	missense	Exon 3 of 4	NP_006040.1	O75971-1
	SNAPC5	NM_001329613.2		c.133A>G	p.Thr45Ala	missense	Exon 2 of 2	NP_001316542.1	O75971-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAPC5	ENST00000316634.6	TSL:1 MANE Select	c.223A>G	p.Thr75Ala	missense	Exon 3 of 3	ENSP00000319597.5	O75971-1
	SNAPC5	ENST00000307979.7	TSL:1	c.133A>G	p.Thr45Ala	missense	Exon 2 of 2	ENSP00000308439.7	O75971-2
	SNAPC5	ENST00000395589.6	TSL:2	c.223A>G	p.Thr75Ala	missense	Exon 3 of 4	ENSP00000378954.2	O75971-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.92	T
PhyloP100		-0.043
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.087
Sift	Benign	0.50	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.024
MutPred		0.13		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

Other links and lift over

dbSNP: rs796052169; hg19: chr15-66786848;