NM_003087.3:c.279G>A

Variant names:

• chr10-86960116-G-A
• rs111800178
• NM_003087.3:c.279G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003087.3(SNCG):​c.279G>A​(p.Gly93Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,612,398 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (26 hom., cov: 33)
  • Exomes 𝑓: 0.00098 (25 hom.)
• Consequence: SNCG NM_003087.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.520

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

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00270769).
• BP6: Variant 10-86960116-G-A is Benign according to our data. Variant chr10-86960116-G-A is described in ClinVar as [Benign]. Clinvar id is 788429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.52 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00939 (1429/152164) while in subpopulation AFR AF= 0.0326 (1352/41512). AF 95% confidence interval is 0.0311. There are 26 homozygotes in gnomad4. There are 682 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCG	NM_003087.3	c.279G>A	p.Gly93Gly	synonymous_variant	Exon 3 of 5	ENST00000372017.4	NP_003078.2
SNCG	NM_001330120.2	c.331G>A	p.Gly111Ser	missense_variant	Exon 5 of 7		NP_001317049.1
SNCG	XM_047425681.1	c.606G>A	p.Gly202Gly	synonymous_variant	Exon 5 of 7		XP_047281637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCG	ENST00000372017.4	c.279G>A	p.Gly93Gly	synonymous_variant	Exon 3 of 5	1	NM_003087.3	ENSP00000361087.3

Frequencies

GnomAD3 genomes AF: 0.00937 AC: 1424 AN: 152046 Hom.: 25 Cov.: 33

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

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: 0.000162

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00242 AC: 602 AN: 248352 Hom.: 14 AF XY: 0.00197 AC XY: 265 AN XY: 134596

Gnomad AFR exome AF: 0.0327

Gnomad AMR exome AF: 0.00151

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000161

Gnomad OTH exome AF: 0.000991

GnomAD4 exome AF: 0.000977 AC: 1426 AN: 1460234 Hom.: 25 Cov.: 33 AF XY: 0.000843 AC XY: 612 AN XY: 726328

Gnomad4 AFR exome AF: 0.0329

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000864

Gnomad4 OTH exome AF: 0.00224

GnomAD4 genome AF: 0.00939 AC: 1429 AN: 152164 Hom.: 26 Cov.: 33 AF XY: 0.00917 AC XY: 682 AN XY: 74384

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.00347

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00349 Hom.: 2

Bravo AF: 0.0108

ESP6500AA AF: 0.0286 AC: 126

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00314 AC: 381

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	0.040
CADD	Benign	6.6
DANN	Benign	0.91
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0027	T
MetaSVM	Uncertain	-0.25	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.23
MVP		0.45
ClinPred		0.025	T
GERP RS		-4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs111800178; hg19: chr10-88719873;