chr6-158017255-C-T

Variant names:

• chr6-158017255-C-T
• rs143362296
• NM_003898.4:c.179C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003898.4(SYNJ2):​c.179C>T​(p.Ala60Val) variant causes a missense change. The variant allele was found at a frequency of 0.00225 in 1,613,908 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0022 (14 hom.)
• Consequence: SYNJ2 NM_003898.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.88
• Publications: 10 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01290378).
• BS2: High Homozygotes in GnomAdExome4 at 14 AR gene

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.179C>T	p.Ala60Val	missense	Exon 2 of 27	NP_003889.1	O15056-1
	SYNJ2	NM_001410947.1		c.179C>T	p.Ala60Val	missense	Exon 2 of 28	NP_001397876.1	O15056-3
	SYNJ2	NM_001178088.2		c.-533C>T		5_prime_UTR	Exon 1 of 26	NP_001171559.1	A0A1W2PR85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2	ENST00000355585.9	TSL:1 MANE Select	c.179C>T	p.Ala60Val	missense	Exon 2 of 27	ENSP00000347792.4	O15056-1
	SYNJ2	ENST00000640338.1	TSL:1	c.179C>T	p.Ala60Val	missense	Exon 2 of 27	ENSP00000492532.1	O15056-3
	SYNJ2	ENST00000638626.1	TSL:1	c.-533C>T		5_prime_UTR	Exon 1 of 26	ENSP00000492369.1	A0A1W2PR85

Frequencies

GnomAD3 genomes AF: 0.00244 AC: 371 AN: 152092 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00782

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00332

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00228 AC: 572 AN: 251190 AF XY: 0.00248

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00533

Gnomad NFE exome AF: 0.00334

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00224 AC: 3267 AN: 1461698 Hom.: 14 Cov.: 31 AF XY: 0.00239 AC XY: 1739 AN XY: 727140

African (AFR) AF: 0.000299 AC: 10 AN: 33474

American (AMR) AF: 0.000470 AC: 21 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00165 AC: 142 AN: 86240

European-Finnish (FIN) AF: 0.00474 AC: 253 AN: 53358

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5766

European-Non Finnish (NFE) AF: 0.00241 AC: 2677 AN: 1111936

Other (OTH) AF: 0.00235 AC: 142 AN: 60384

GnomAD4 genome AF: 0.00244 AC: 371 AN: 152210 Hom.: 0 Cov.: 31 AF XY: 0.00247 AC XY: 184 AN XY: 74414

African (AFR) AF: 0.000506 AC: 21 AN: 41522

American (AMR) AF: 0.000981 AC: 15 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.00782 AC: 83 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00332 AC: 226 AN: 67998

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00279 Hom.: 3

Bravo AF: 0.00184

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00279 AC: 24

ExAC AF: 0.00242 AC: 294

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00327

EpiControl AF: 0.00255

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Meniere disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.63	D
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.42
Sift	Benign	0.15	T
Sift4G	Uncertain	0.047	D
Polyphen		1.0	D
Vest4		0.86
MVP		0.53
MPC		0.23
ClinPred		0.024	T
GERP RS		5.1
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.46
Mutation Taster		=94/6	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: rs143362296; hg19: chr6-158438287; COSMIC: COSV62895925; COSMIC: COSV62895925;