Variant chr6-157982086-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003898.4(SYNJ2):c.125T>C(p.Leu42Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000339 in 1,181,620 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SYNJ2
NM_003898.4 missense, splice_region

Scores

Splicing: ADA: 0.0006886

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.825

Variant links:

Genes affected

SYNJ2 (HGNC:11504): (synaptojanin 2) The gene is a member of the inositol-polyphosphate 5-phosphatase family. The encoded protein interacts with the ras-related C3 botulinum toxin substrate 1, which causes translocation of the encoded protein to the plasma membrane where it inhibits clathrin-mediated endocytosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

SYNJ2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ2	NM_003898.4 link	c.125T>C	p.Leu42Pro	missense_variant, splice_region_variant	1/27	ENST00000355585.9	NP_003889.1	O15056-1B4DG94

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SYNJ2	ENST00000355585.9 link	c.125T>C	p.Leu42Pro	missense_variant, splice_region_variant	1/27	1	NM_003898.4	ENSP00000347792.4	O15056-1
SYNJ2	ENST00000640338.1 link	c.125T>C	p.Leu42Pro	missense_variant, splice_region_variant	1/27	1		ENSP00000492532.1	O15056-3
SYNJ2	ENST00000367113.5 link	c.47T>C	p.Leu16Pro	missense_variant, splice_region_variant	1/4	2		ENSP00000356080.4	H7BY56

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000339

AC:

AN:

1181620

Hom.:

Cov.:

AF XY:

0.00000524

AC XY:

AN XY:

572946

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:

0.00000410

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

Jul 02, 2024

The c.125T>C (p.L42P) alteration is located in exon 1 (coding exon 1) of the SYNJ2 gene. This alteration results from a T to C substitution at nucleotide position 125, causing the leucine (L) at amino acid position 42 to be replaced by a proline (P). 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

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.79

D;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.44

T;T

M_CAP

Pathogenic

0.97

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

2.0

M;M

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-5.1

D;.

REVEL

Uncertain

0.59

Sift

Uncertain

0.017

D;.

Sift4G

Uncertain

0.044

D;.

Polyphen

0.0010

B;B

Vest4

0.45

MutPred

0.49

Gain of disorder (P = 0.0187);Gain of disorder (P = 0.0187);

MVP

0.97

MPC

0.31

ClinPred

0.80

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.94

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00069

dbscSNV1_RF

Benign

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over