Genetic Variant NM_006372.5:c.1564G>T (chr6-85615064-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_006372.5(SYNCRIP):c.1564G>T(p.Gly522Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,886 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. G522S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SYNCRIP
NM_006372.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.97

Publications

2 publications found

Variant links:

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

SYNCRIP links:

ENSG00000271793 (HGNC:):

ENSG00000271793 links:

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ACMG classification

Classification was made for transcript

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_006372.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SYNCRIP	NM_006372.5	MANE Select	c.1564G>T	p.Gly522Cys	missense	Exon 11 of 11	NP_006363.4
SYNCRIP	NM_001439158.1		c.1564G>T	p.Gly522Cys	missense	Exon 11 of 12	NP_001426087.1
SYNCRIP	NM_001439161.1		c.1564G>T	p.Gly522Cys	missense	Exon 11 of 12	NP_001426090.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYNCRIP	ENST00000369622.8	TSL:1 MANE Select	c.1564G>T	p.Gly522Cys	missense	Exon 11 of 11	ENSP00000358635.3	O60506-1
SYNCRIP	ENST00000355238.11	TSL:1	c.1564G>T	p.Gly522Cys	missense	Exon 11 of 12	ENSP00000347380.6	O60506-3
SYNCRIP	ENST00000616122.5	TSL:1	c.1270G>T	p.Gly424Cys	missense	Exon 10 of 11	ENSP00000484577.1	B7Z645

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000671

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.7

PhyloP100

5.0

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.32

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

0.95

Vest4

0.78

MutPred

0.42

Gain of sheet (P = 0.0149)

MVP

0.71

MPC

0.88

ClinPred

0.99

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.38

gMVP

0.84

Mutation Taster

=36/64

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over