chr6-157982083-C-T

Variant names:

• chr6-157982083-C-T
• rs1449894549
• NM_003898.4:c.122C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003898.4(SYNJ2):​c.122C>T​(p.Thr41Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000846 in 1,182,078 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: SYNJ2 NM_003898.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.95
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003898.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2	NM_003898.4	MANE Select	c.122C>T	p.Thr41Met	missense	Exon 1 of 27	NP_003889.1	O15056-1
	SYNJ2	NM_001410947.1		c.122C>T	p.Thr41Met	missense	Exon 1 of 28	NP_001397876.1	O15056-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2	ENST00000355585.9	TSL:1 MANE Select	c.122C>T	p.Thr41Met	missense	Exon 1 of 27	ENSP00000347792.4	O15056-1
	SYNJ2	ENST00000640338.1	TSL:1	c.122C>T	p.Thr41Met	missense	Exon 1 of 27	ENSP00000492532.1	O15056-3
	SYNJ2	ENST00000367113.5	TSL:2	c.44C>T	p.Thr15Met	missense	Exon 1 of 4	ENSP00000356080.4	H7BY56

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.46e-7 AC: 1 AN: 1182078 Hom.: 0 Cov.: 30 AF XY: 0.00000174 AC XY: 1 AN XY: 573312

African (AFR) AF: 0.0000422 AC: 1 AN: 23704

American (AMR) AF: 0.00 AC: 0 AN: 10626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16762

East Asian (EAS) AF: 0.00 AC: 0 AN: 27090

South Asian (SAS) AF: 0.00 AC: 0 AN: 48432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3370

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 976368

Other (OTH) AF: 0.00 AC: 0 AN: 47694

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.4	L
PhyloP100		1.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.13	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.028	D
Polyphen		0.81	P
Vest4		0.19
MutPred		0.40		Loss of glycosylation at T41 (P = 0.0371)
MVP		0.85
MPC		0.41
ClinPred		0.94	D
GERP RS		3.1
PromoterAI		0.30	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.15
gMVP		0.31
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1449894549; hg19: chr6-158403115;