Variant 14-74409681-G-A details in Genebe, Genetics Data Aggregator

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

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]

SYNDIG1L links:

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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
SYNDIG1L	NM_001105579.2 linkuse as main transcript	c.64C>T	p.Pro22Ser	missense_variant	2/4	ENST00000331628.8	NP_001099049.1
SYNDIG1L	XM_017021600.2 linkuse as main transcript	c.64C>T	p.Pro22Ser	missense_variant	2/4		XP_016877089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SYNDIG1L	ENST00000331628.8 linkuse as main transcript	c.64C>T	p.Pro22Ser	missense_variant	2/4	5	NM_001105579.2	ENSP00000331474	P1
SYNDIG1L	ENST00000554823.1 linkuse as main transcript	c.64C>T	p.Pro22Ser	missense_variant	1/3	3		ENSP00000450439	P1
SYNDIG1L	ENST00000554953.1 linkuse as main transcript	c.64C>T	p.Pro22Ser	missense_variant	2/2	2		ENSP00000451519

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1333538

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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.:

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 submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The 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

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

LIST_S2

Benign

0.57

T;.;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.072

T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.3

L;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

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

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.

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