chr11-45252661-C-T

Variant names:

• chr11-45252661-C-T
• rs149737973
• NM_020826.3:c.606G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020826.3(SYT13):​c.606G>A​(p.Arg202Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,006 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: SYT13 NM_020826.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507
• Publications: 3 publications found

Genes affected

SYT13 (HGNC:14962): (synaptotagmin 13) This gene encodes a member of the large synaptotagmin protein family. Family members have an extracellular N-terminal transmembrane domain and a cytoplasmic C terminus with two tandem C2 domains (C2A and C2B). Synaptotogmin family members can form homo- and heteromeric complexes with each other. They also have different biochemical properties and developmental profiles, and patterns of tissue distribution. Synaptotagmins function as membrane traffickers in multicellular organisms. Two alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

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 (REVEL=0.008).
• BP7: Synonymous conserved (PhyloP=0.507 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020826.3. 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
	SYT13	NM_020826.3	MANE Select	c.606G>A	p.Arg202Arg	synonymous	Exon 4 of 6	NP_065877.1	Q7L8C5
	SYT13	NM_001247987.2		c.174G>A	p.Arg58Arg	synonymous	Exon 6 of 8	NP_001234916.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT13	ENST00000020926.8	TSL:1 MANE Select	c.606G>A	p.Arg202Arg	synonymous	Exon 4 of 6	ENSP00000020926.3	Q7L8C5
	SYT13	ENST00000533332.1	TSL:1	n.*623G>A		non_coding_transcript_exon	Exon 6 of 8	ENSP00000434967.1	H0YE47
	SYT13	ENST00000533332.1	TSL:1	n.*623G>A		3_prime_UTR	Exon 6 of 8	ENSP00000434967.1	H0YE47

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459006 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725196

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39596

South Asian (SAS) AF: 0.00 AC: 0 AN: 86118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109776

Other (OTH) AF: 0.00 AC: 0 AN: 60244

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.3
DANN	Benign	0.57
PhyloP100		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs149737973; hg19: chr11-45274212;