16-1992092-C-T

Variant names:

• chr16-1992092-C-T
• NM_004209.6:c.218C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_004209.6(SYNGR3):​c.218C>T​(p.Ala73Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYNGR3 NM_004209.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

Genes affected

SYNGR3 (HGNC:11501): (synaptogyrin 3) This gene encodes an integral membrane protein. The exact function of this protein is unclear, but studies of a similar murine protein suggest that it is a synaptic vesicle protein that also interacts with the dopamine transporter. The gene product belongs to the synaptogyrin gene family. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22545692).
• BP6: Variant 16-1992092-C-T is Benign according to our data. Variant chr16-1992092-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2278376.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNGR3	NM_004209.6	c.218C>T	p.Ala73Val	missense_variant	Exon 2 of 4	ENST00000248121.7	NP_004200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNGR3	ENST00000248121.7	c.218C>T	p.Ala73Val	missense_variant	Exon 2 of 4	1	NM_004209.6	ENSP00000248121.2
SYNGR3	ENST00000568896.1	c.338C>T	p.Ala113Val	missense_variant	Exon 3 of 4	5		ENSP00000454756.1
SYNGR3	ENST00000563869.1	c.150C>T	p.Arg50Arg	synonymous_variant	Exon 2 of 4	2		ENSP00000455344.1
SYNGR3	ENST00000562045	c.-48C>T		5_prime_UTR_variant	Exon 1 of 3	2		ENSP00000455577.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1423438 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 704732

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 11, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T;.;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.59	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.6	N;.;N
REVEL	Benign	0.11
Sift	Benign	0.17	T;.;T
Sift4G	Benign	0.10	T;T;T
Polyphen		0.066	B;.;.
Vest4		0.19
MutPred		0.62		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);.;
MVP		0.15
MPC		0.63
ClinPred		0.36	T
GERP RS		1.4
Varity_R		0.049
gMVP		0.40

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-2042093;