rs79356259

Positions:

• chr17-37516711-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007247.6(SYNRG):​c.*2229G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 150,476 control chromosomes in the GnomAD database, including 816 homozygotes. 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: 𝑓 0.097 (816 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYNRG NM_007247.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

SYNRG (HGNC:557): (synergin gamma) This gene encodes a protein that interacts with the gamma subunit of AP1 clathrin-adaptor complex. The AP1 complex is located at the trans-Golgi network and associates specific proteins with clathrin-coated vesicles. This encoded protein may act to connect the AP1 complex to other proteins. Alternatively spliced transcript variants that encode different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNRG	NM_007247.6	c.*2229G>A		3_prime_UTR_variant	22/22	ENST00000612223.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNRG	ENST00000612223.5	c.*2229G>A		3_prime_UTR_variant	22/22	1	NM_007247.6	P4
SYNRG	ENST00000612641.1	n.156+476G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 14629 AN: 150364 Hom.: 814 Cov.: 30

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.0940

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0880

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.110

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0972 AC: 14626 AN: 150476 Hom.: 816 Cov.: 30 AF XY: 0.0977 AC XY: 7164 AN XY: 73294

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0865

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0880

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.110

Alfa AF: 0.101 Hom.: 106

Bravo AF: 0.0979

Asia WGS AF: 0.148 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.2
DANN	Benign	0.89

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

LitVar

Other links and lift over

dbSNP: rs79356259; hg19: chr17-35876814;