20-24543233-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024893.3(SYNDIG1):​c.136C>A​(p.Pro46Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SYNDIG1
NM_024893.3 missense

Scores

6
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.63
Variant links:
Genes affected
SYNDIG1 (HGNC:15885): (synapse differentiation inducing 1) This gene encodes a protein that belongs to the interferon-induced transmembrane family of proteins. A similar protein in rat is thought to regulate the development of excitatory synapses. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNDIG1NM_024893.3 linkc.136C>A p.Pro46Thr missense_variant Exon 2 of 4 ENST00000376862.4 NP_079169.1 Q9H7V2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNDIG1ENST00000376862.4 linkc.136C>A p.Pro46Thr missense_variant Exon 2 of 4 1 NM_024893.3 ENSP00000366058.3 Q9H7V2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461658
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
727148
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.136C>A (p.P46T) alteration is located in exon 2 (coding exon 1) of the SYNDIG1 gene. This alteration results from a C to A substitution at nucleotide position 136, causing the proline (P) at amino acid position 46 to be replaced by a threonine (T). 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
0.13
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.91
D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.79
D
MetaSVM
Pathogenic
0.81
D
MutationAssessor
Uncertain
2.7
M
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-2.6
D
REVEL
Uncertain
0.56
Sift
Uncertain
0.012
D
Sift4G
Uncertain
0.022
D
Polyphen
1.0
D
Vest4
0.67
MutPred
0.33
Gain of glycosylation at P46 (P = 0.0871);
MVP
0.85
MPC
0.99
ClinPred
0.96
D
GERP RS
6.0
Varity_R
0.24
gMVP
0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-24523869; API