NM_006372.5:c.1640_1641delGCinsAT

Variant names:

• chr6-85614987-GC-AT
• NM_006372.5:c.1640_1641delGCinsAT
• SYNCRIP p.Gly547Asp

Variant summary

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

The NM_006372.5(SYNCRIP):​c.1640_1641delGCinsAT​(p.Gly547Asp) 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. G547V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYNCRIP NM_006372.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.73
• Publications: 0 publications found

Genes affected

SYNCRIP (HGNC:16918): (synaptotagmin binding cytoplasmic RNA interacting protein) This gene encodes a member of the cellular heterogeneous nuclear ribonucleoprotein (hnRNP) family. hnRNPs are RNA binding proteins that complex with heterogeneous nuclear RNA (hnRNA) and regulate alternative splicing, polyadenylation, and other aspects of mRNA metabolism and transport. The encoded protein plays a role in multiple aspects of mRNA maturation and is associated with several multiprotein complexes including the apoB RNA editing-complex and survival of motor neurons (SMN) complex. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 20. [provided by RefSeq, Dec 2011]

SYNCRIP Gene-Disease associations (from GenCC):

• SYNCRIP-related neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: ClinGen, G2P
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

ENSG00000271793 (HGNC:):

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_006372.5. 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
	SYNCRIP	NM_006372.5	MANE Select	c.1640_1641delGCinsAT	p.Gly547Asp	missense	N/A	NP_006363.4
	SYNCRIP	NM_001439158.1		c.1640_1641delGCinsAT	p.Gly547Asp	missense	N/A	NP_001426087.1
	SYNCRIP	NM_001439161.1		c.1640_1641delGCinsAT	p.Gly547Asp	missense	N/A	NP_001426090.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNCRIP	ENST00000369622.8	TSL:1 MANE Select	c.1640_1641delGCinsAT	p.Gly547Asp	missense	N/A	ENSP00000358635.3	O60506-1
	SYNCRIP	ENST00000355238.11	TSL:1	c.1640_1641delGCinsAT	p.Gly547Asp	missense	N/A	ENSP00000347380.6	O60506-3
	SYNCRIP	ENST00000616122.5	TSL:1	c.1346_1347delGCinsAT	p.Gly449Asp	missense	N/A	ENSP00000484577.1	B7Z645

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		7.7

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: chr6-86324705;