22-39374547-G-T

Position:

• chr22-39374547-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000328933.10(SYNGR1):​c.331G>T​(p.Val111Phe) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYNGR1 ENST00000328933.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.74

Genes affected

SYNGR1 (HGNC:11498): (synaptogyrin 1) This gene encodes an integral membrane protein associated with presynaptic vesicles in neuronal cells. The exact function of this protein is unclear, but studies of a similar murine protein suggest that it functions in synaptic plasticity without being required for synaptic transmission. The gene product belongs to the synaptogyrin gene family. Three alternatively spliced variants encoding three different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39018232).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNGR1	NM_004711.5	c.331G>T	p.Val111Phe	missense_variant	2/4	ENST00000328933.10	NP_004702.2
SYNGR1	NM_145738.3	c.334G>T	p.Val112Phe	missense_variant	2/4		NP_663791.1
SYNGR1	NM_145731.4	c.331G>T	p.Val111Phe	missense_variant	2/4		NP_663783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNGR1	ENST00000328933.10	c.331G>T	p.Val111Phe	missense_variant	2/4	1	NM_004711.5	ENSP00000332287	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.331G>T (p.V111F) alteration is located in exon 2 (coding exon 2) of the SYNGR1 gene. This alteration results from a G to T substitution at nucleotide position 331, causing the valine (V) at amino acid position 111 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.092	.;.;.;T;.
Eigen	Benign	-0.083
Eigen_PC	Benign	-0.066
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.39	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.56	N;.;.;N;.
MutationTaster	Benign	1.0	D;D;D;D;D
PROVEAN	Benign	2.0	N;N;N;N;N
REVEL	Benign	0.22
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.99	D;.;.;D;D
Vest4		0.56
MutPred		0.61		Loss of glycosylation at S107 (P = 0.1488);Loss of glycosylation at S107 (P = 0.1488);Loss of glycosylation at S107 (P = 0.1488);Loss of glycosylation at S107 (P = 0.1488);.;
MVP		0.31
MPC		0.64
ClinPred		0.87	D
GERP RS		3.1
Varity_R		0.073
gMVP		0.96

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: chr22-39770552;