17-37540508-C-T

Variant names:

• chr17-37540508-C-T
• NM_007247.6:c.3238G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007247.6(SYNRG):​c.3238G>A​(p.Glu1080Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SYNRG NM_007247.6 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.88
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007247.6. 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
	SYNRG	NM_007247.6	MANE Select	c.3238G>A	p.Glu1080Lys	missense	Exon 16 of 22	NP_009178.3
	SYNRG	NM_001405103.1		c.3541G>A	p.Glu1181Lys	missense	Exon 17 of 24	NP_001392032.1
	SYNRG	NM_198882.3		c.3004G>A	p.Glu1002Lys	missense	Exon 15 of 22	NP_942583.1	Q9UMZ2-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNRG	ENST00000612223.5	TSL:1 MANE Select	c.3238G>A	p.Glu1080Lys	missense	Exon 16 of 22	ENSP00000483453.1	Q9UMZ2-1
	SYNRG	ENST00000622045.4	TSL:1	c.3004G>A	p.Glu1002Lys	missense	Exon 15 of 22	ENSP00000483063.1	Q9UMZ2-7
	SYNRG	ENST00000619541.4	TSL:1	c.3001G>A	p.Glu1001Lys	missense	Exon 15 of 21	ENSP00000477885.1	Q9UMZ2-8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	SYNRG-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.81	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.32		Gain of MoRF binding (P = 0.0045)
MVP		0.12
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.45
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.40		Position offset: 35

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr17-35900610;