10-86960057-G-A

Variant names:

• chr10-86960057-G-A
• rs144819543
• NM_003087.3:c.220G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003087.3(SNCG):​c.220G>A​(p.Val74Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000264 in 1,612,992 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (1 hom.)
• Consequence: SNCG NM_003087.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71
• Publications: 3 publications found

Genes affected

SNCG (HGNC:11141): (synuclein gamma) This gene encodes a member of the synuclein family of proteins which are believed to be involved in the pathogenesis of neurodegenerative diseases. Mutations in this gene have also been associated with breast tumor development. [provided by RefSeq, Jan 2010]

MMRN2 (HGNC:19888): (multimerin 2) This gene encodes a protein belonging to the member of elastin microfibril interface-located (EMILIN) protein family. This family member is an extracellular matrix glycoprotein that can interfere with tumor angiogenesis and growth. It serves as a transforming growth factor beta antagonist and can interfere with the VEGF-A/VEGFR2 pathway. A related pseudogene has been identified on chromosome 6. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07044056).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003087.3. 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
	SNCG	NM_003087.3	MANE Select	c.220G>A	p.Val74Ile	missense	Exon 3 of 5	NP_003078.2	O76070
	SNCG	NM_001330120.2		c.272G>A	p.Arg91His	missense	Exon 5 of 7	NP_001317049.1	F8W754

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNCG	ENST00000372017.4	TSL:1 MANE Select	c.220G>A	p.Val74Ile	missense	Exon 3 of 5	ENSP00000361087.3	O76070
	SNCG	ENST00000930521.1		c.220G>A	p.Val74Ile	missense	Exon 4 of 6	ENSP00000600580.1
	SNCG	ENST00000951192.1		c.220G>A	p.Val74Ile	missense	Exon 5 of 7	ENSP00000621251.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000101 AC: 25 AN: 248166 AF XY: 0.000119

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000196

Gnomad OTH exome AF: 0.000332

GnomAD4 exome AF: 0.000282 AC: 412 AN: 1460700 Hom.: 1 Cov.: 33 AF XY: 0.000277 AC XY: 201 AN XY: 726610

African (AFR) AF: 0.0000896 AC: 3 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39686

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000338 AC: 376 AN: 1111736

Other (OTH) AF: 0.000481 AC: 29 AN: 60348

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152292 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74464

African (AFR) AF: 0.00 AC: 0 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000199 Hom.: 0

Bravo AF: 0.000113

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000140 AC: 17

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000178

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	0.12
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.0049
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.070	T
MetaSVM	Uncertain	-0.20	T
PhyloP100		5.7
PROVEAN	Benign	0.19	N
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.033	D
Vest4		0.26
MVP		0.64
ClinPred		0.091	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144819543; hg19: chr10-88719814;