7-106093047-C-T

Variant names:

• chr7-106093047-C-T
• NM_182715.4:c.493G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182715.4(SYPL1):​c.493G>A​(p.Gly165Ser) 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. 16/22 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: SYPL1 NM_182715.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39
• Publications: 0 publications found

Genes affected

SYPL1 (HGNC:11507): (synaptophysin like 1) Predicted to be involved in chemical synaptic transmission. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12671027).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182715.4. 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
	SYPL1	NM_182715.4	MANE Select	c.493G>A	p.Gly165Ser	missense	Exon 4 of 5	NP_874384.1	Q16563-2
	SYPL1	NM_001381910.1		c.625G>A	p.Gly209Ser	missense	Exon 6 of 7	NP_001368839.1	A0A994J846
	SYPL1	NM_001381911.1		c.571G>A	p.Gly191Ser	missense	Exon 5 of 6	NP_001368840.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYPL1	ENST00000455385.7	TSL:1 MANE Select	c.493G>A	p.Gly165Ser	missense	Exon 4 of 5	ENSP00000388336.2	Q16563-2
	SYPL1	ENST00000011473.6	TSL:1	c.547G>A	p.Gly183Ser	missense	Exon 5 of 6	ENSP00000011473.2	Q16563-1
	SYPL1	ENST00000460770.1	TSL:1	n.206G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.097
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.4
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.032
Sift	Benign	0.52	T
Sift4G	Benign	0.72	T
Polyphen		0.57	P
Vest4		0.21
MutPred		0.45		Gain of glycosylation at T182 (P = 0.1346)
MVP		0.095
MPC		0.47
ClinPred		0.75	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.047
gMVP		0.64
Mutation Taster		=76/24	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

hg19: chr7-105733493;