1-32695525-C-T

Variant names:

• chr1-32695525-C-T
• NM_030786.3:c.573G>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_030786.3(SYNC):​c.573G>A​(p.Glu191Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,526 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: 28)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SYNC NM_030786.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.571

Genes affected

SYNC (HGNC:28897): (syncoilin, intermediate filament protein) This gene encodes a member of the intermediate filament family which contains an N-terminal head domain, followed by a central coiled-coil region and a short C-terminal tail. The protein is highly expressed in skeletal and cardiac muscle. The protein links the dystrophin associated protein complex (DAPC) to desmin filaments in muscle and may have a structural role in striated muscle. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=0.571 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNC	NM_030786.3	c.573G>A	p.Glu191Glu	synonymous_variant	Exon 2 of 5	ENST00000409190.8	NP_110413.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNC	ENST00000409190.8	c.573G>A	p.Glu191Glu	synonymous_variant	Exon 2 of 5	2	NM_030786.3	ENSP00000386439.3
SYNC	ENST00000373484.4	c.573G>A	p.Glu191Glu	synonymous_variant	Exon 2 of 4	2		ENSP00000362583.3
SYNC	ENST00000417633.1	c.*40G>A		downstream_gene_variant		4		ENSP00000401975.1
SYNC	ENST00000426909.1	c.*98G>A		downstream_gene_variant		4		ENSP00000387594.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399526 Hom.: 0 Cov.: 98 AF XY: 0.00000435 AC XY: 3 AN XY: 690274

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000560

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.7
DANN	Benign	0.86

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-33161126;