6-85615025-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006372.5(SYNCRIP):c.1603G>A(p.Val535Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000209 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

SYNCRIP
NM_006372.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.72

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 links:

ENSG00000271793 (HGNC:):

ENSG00000271793 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.038567543).

BS2

High AC in GnomAd4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNCRIP	NM_006372.5 link	c.1603G>A	p.Val535Ile	missense_variant	Exon 11 of 11	ENST00000369622.8	NP_006363.4	O60506-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNCRIP	ENST00000369622.8 link	c.1603G>A	p.Val535Ile	missense_variant	Exon 11 of 11	1	NM_006372.5	ENSP00000358635.3		O60506-1
ENSG00000271793	ENST00000682083.1 link	n.1603G>A		non_coding_transcript_exon_variant	Exon 11 of 40			ENSP00000506859.1

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000131

AC:

AN:

251194

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000212

AC:

310

AN:

1461742

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

143

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000257

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000177

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000254

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Nov 08, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1603G>A (p.V535I) alteration is located in exon 11 (coding exon 10) of the SYNCRIP gene. This alteration results from a G to A substitution at nucleotide position 1603, causing the valine (V) at amino acid position 535 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.0054

T;.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

0.0084

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.86

D;D;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.039

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.46

.;N;N

REVEL

Benign

0.10

Sift

Benign

1.0

.;T;T

Sift4G

Benign

0.42

T;T;T

Polyphen

0.071

B;B;B

Vest4

0.32

MutPred

0.25

.;Gain of catalytic residue at V535 (P = 0.104);Gain of catalytic residue at V535 (P = 0.104);

MVP

0.34

MPC

0.67

ClinPred

0.021

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.054

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over