17-37542048-GG-AT

Variant names:

• chr17-37542048-GG-AT
• NM_007247.6:c.3125_3126delCCinsAT
• SYNRG p.Ala1042Asp

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_007247.6(SYNRG):​c.3125_3126delCCinsAT​(p.Ala1042Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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)
• Consequence: SYNRG NM_007247.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.16
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.3125_3126delCCinsAT	p.Ala1042Asp	missense	N/A	NP_009178.3
	SYNRG	NM_001405103.1		c.3428_3429delCCinsAT	p.Ala1143Asp	missense	N/A	NP_001392032.1
	SYNRG	NM_198882.3		c.2891_2892delCCinsAT	p.Ala964Asp	missense	N/A	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.3125_3126delCCinsAT	p.Ala1042Asp	missense	N/A	ENSP00000483453.1	Q9UMZ2-1
	SYNRG	ENST00000622045.4	TSL:1	c.2891_2892delCCinsAT	p.Ala964Asp	missense	N/A	ENSP00000483063.1	Q9UMZ2-7
	SYNRG	ENST00000619541.4	TSL:1	c.2888_2889delCCinsAT	p.Ala963Asp	missense	N/A	ENSP00000477885.1	Q9UMZ2-8

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-35902150;