7-106097834-A-T

Variant names:

• chr7-106097834-A-T
• NM_182715.4:c.258T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182715.4(SYPL1):​c.258T>A​(p.Asp86Glu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SYPL1 NM_182715.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.13

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076930165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYPL1	NM_182715.4	c.258T>A	p.Asp86Glu	missense_variant	Exon 3 of 5	ENST00000455385.7	NP_874384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYPL1	ENST00000455385.7	c.258T>A	p.Asp86Glu	missense_variant	Exon 3 of 5	1	NM_182715.4	ENSP00000388336.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.312T>A (p.D104E) alteration is located in exon 4 (coding exon 4) of the SYPL1 gene. This alteration results from a T to A substitution at nucleotide position 312, causing the aspartic acid (D) at amino acid position 104 to be replaced by a glutamic acid (E). 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	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.0030
DANN	Benign	0.26
DEOGEN2	Benign	0.018	.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.21	T;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.077	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.12	N;N;N
REVEL	Benign	0.046
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0010	.;B;.
Vest4		0.082
MutPred		0.35		.;Gain of ubiquitination at K103 (P = 0.0961);.;
MVP		0.11
MPC		0.11
ClinPred		0.023	T
GERP RS		-11
Varity_R		0.034
gMVP		0.41

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: chr7-105738280;