chr17-37542049-G-T

Variant names:

• chr17-37542049-G-T
• rs1365047959
• NM_007247.6:c.3125C>A

Variant summary

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

The NM_007247.6(SYNRG):​c.3125C>A​(p.Ala1042Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1042V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SYNRG NM_007247.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.16
• Publications: 1 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.3125C>A	p.Ala1042Asp	missense	Exon 15 of 22	NP_009178.3
	SYNRG	NM_001405103.1		c.3428C>A	p.Ala1143Asp	missense	Exon 16 of 24	NP_001392032.1
	SYNRG	NM_198882.3		c.2891C>A	p.Ala964Asp	missense	Exon 14 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.3125C>A	p.Ala1042Asp	missense	Exon 15 of 22	ENSP00000483453.1	Q9UMZ2-1
	SYNRG	ENST00000622045.4	TSL:1	c.2891C>A	p.Ala964Asp	missense	Exon 14 of 22	ENSP00000483063.1	Q9UMZ2-7
	SYNRG	ENST00000619541.4	TSL:1	c.2888C>A	p.Ala963Asp	missense	Exon 14 of 21	ENSP00000477885.1	Q9UMZ2-8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 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: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		8.2
PrimateAI	Pathogenic	0.79	T
Sift4G	Uncertain	0.027	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.39		Loss of sheet (P = 0.0104)
MVP		0.42
ClinPred		0.97	D
GERP RS		6.0
PromoterAI		-0.010	Neutral
Varity_R		0.51
gMVP		0.55
Mutation Taster		=63/37	polymorphism

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: rs1365047959; hg19: chr17-35902151;