1-109476817-A-T

Variant names:

• chr1-109476817-A-T
• rs62623713
• NM_001040709.2:c.296A>T

Variant summary

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

The NM_001040709.2(SYPL2):​c.296A>T​(p.Glu99Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SYPL2 NM_001040709.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.857
• Publications: 0 publications found

Genes affected

SYPL2 (HGNC:27638): (synaptophysin like 2) Involved in substantia nigra development. Predicted to be integral component of membrane. Predicted to be active in synaptic vesicle membrane. [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=0.074314415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYPL2	NM_001040709.2	c.296A>T	p.Glu99Val	missense_variant	Exon 4 of 6	ENST00000369872.4	NP_001035799.1
SYPL2	XM_011541283.3	c.296A>T	p.Glu99Val	missense_variant	Exon 4 of 7		XP_011539585.1
SYPL2	XM_011541284.3	c.296A>T	p.Glu99Val	missense_variant	Exon 4 of 6		XP_011539586.1
SYPL2	XM_011541285.2	c.296A>T	p.Glu99Val	missense_variant	Exon 4 of 5		XP_011539587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYPL2	ENST00000369872.4	c.296A>T	p.Glu99Val	missense_variant	Exon 4 of 6	1	NM_001040709.2	ENSP00000358888.3
SYPL2	ENST00000475497.1	n.506A>T		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.29	N
PhyloP100		0.86
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.030
Sift	Benign	0.20	T
Sift4G	Benign	0.22	T
Polyphen		0.022	B
Vest4		0.24
MutPred		0.37		Loss of solvent accessibility (P = 0.0022);
MVP		0.16
MPC		0.38
ClinPred		0.35	T
GERP RS		3.3
Varity_R		0.13
gMVP		0.62
Mutation Taster		=95/5	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

dbSNP: rs62623713; hg19: chr1-110019439;