NM_001030005.3:c.172C>A

Variant names:

• chr15-74828041-C-A
• rs780059071
• NM_001030005.3:c.172C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001030005.3(CPLX3):​c.172C>A​(p.Arg58Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CPLX3 NM_001030005.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.358
• Publications: 0 publications found

Genes affected

CPLX3 (HGNC:27652): (complexin 3) Predicted to enable SNARE binding activity. Predicted to be involved in regulation of neurotransmitter secretion and synaptic vesicle exocytosis. Predicted to be located in plasma membrane and synapse. Predicted to be part of SNARE complex. Predicted to be active in photoreceptor ribbon synapse and terminal bouton. Predicted to be anchored component of presynaptic active zone membrane and anchored component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000261606 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP7: Synonymous conserved (PhyloP=0.358 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030005.3. 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
	CPLX3	NM_001030005.3	MANE Select	c.172C>A	p.Arg58Arg	synonymous	Exon 2 of 3	NP_001025176.1	Q8WVH0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLX3	ENST00000395018.6	TSL:1 MANE Select	c.172C>A	p.Arg58Arg	synonymous	Exon 2 of 3	ENSP00000378464.4	Q8WVH0
	ENSG00000261606	ENST00000488000.6	TSL:2	n.3381C>A		non_coding_transcript_exon	Exon 13 of 14
	ENSG00000261606	ENST00000564823.1	TSL:2	n.3610C>A		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453624 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 722184

African (AFR) AF: 0.00 AC: 0 AN: 33332

American (AMR) AF: 0.00 AC: 0 AN: 43830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25968

East Asian (EAS) AF: 0.00 AC: 0 AN: 39422

South Asian (SAS) AF: 0.00 AC: 0 AN: 84584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107984

Other (OTH) AF: 0.00 AC: 0 AN: 60044

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs780059071; hg19: chr15-75120382;