chr14-74409681-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001105579.2(SYNDIG1L):​c.64C>T​(p.Pro22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SYNDIG1L
NM_001105579.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.186
Variant links:
Genes affected
SYNDIG1L (HGNC:32388): (synapse differentiation inducing 1 like) Predicted to be located in Golgi apparatus. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle and membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.071576566).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SYNDIG1LNM_001105579.2 linkuse as main transcriptc.64C>T p.Pro22Ser missense_variant 2/4 ENST00000331628.8 NP_001099049.1
SYNDIG1LXM_017021600.2 linkuse as main transcriptc.64C>T p.Pro22Ser missense_variant 2/4 XP_016877089.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SYNDIG1LENST00000331628.8 linkuse as main transcriptc.64C>T p.Pro22Ser missense_variant 2/45 NM_001105579.2 ENSP00000331474 P1
SYNDIG1LENST00000554823.1 linkuse as main transcriptc.64C>T p.Pro22Ser missense_variant 1/33 ENSP00000450439 P1
SYNDIG1LENST00000554953.1 linkuse as main transcriptc.64C>T p.Pro22Ser missense_variant 2/22 ENSP00000451519

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1333538
Hom.:
0
Cov.:
46
AF XY:
0.00
AC XY:
0
AN XY:
651868
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 08, 2024The c.64C>T (p.P22S) alteration is located in exon 2 (coding exon 1) of the SYNDIG1L gene. This alteration results from a C to T substitution at nucleotide position 64, causing the proline (P) at amino acid position 22 to be replaced by a serine (S). 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
0.070
BayesDel_addAF
Benign
-0.066
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
7.0
DANN
Benign
0.30
DEOGEN2
Benign
0.0026
T;T;.
Eigen
Benign
-0.96
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.084
N
LIST_S2
Benign
0.57
T;.;T
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.072
T;T;T
MetaSVM
Benign
-0.49
T
MutationAssessor
Benign
1.3
L;L;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.70
N;N;N
REVEL
Benign
0.17
Sift
Benign
0.49
T;T;T
Sift4G
Benign
0.84
T;T;T
Polyphen
0.0010
B;B;.
Vest4
0.034
MutPred
0.18
Gain of catalytic residue at Y25 (P = 0.0112);Gain of catalytic residue at Y25 (P = 0.0112);Gain of catalytic residue at Y25 (P = 0.0112);
MVP
0.33
MPC
0.29
ClinPred
0.090
T
GERP RS
2.5
Varity_R
0.039
gMVP
0.26

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

LitVar

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

Other links and lift over

dbSNP: rs952683048; hg19: chr14-74876384; API