chr7-106097727-G-A

Variant names:

• chr7-106097727-G-A
• rs1044673352
• NM_182715.4:c.365C>T

Variant summary

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

The NM_001381917.1(SYPL1):​c.-32C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SYPL1 NM_001381917.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.801
• 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=0.07131103).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001381917.1. 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.365C>T	p.Thr122Met	missense	Exon 3 of 5	NP_874384.1	Q16563-2
	SYPL1	NM_001381917.1		c.-32C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	NP_001368846.1
	SYPL1	NM_001381910.1		c.497C>T	p.Thr166Met	missense	Exon 5 of 7	NP_001368839.1	A0A994J846

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYPL1	ENST00000455385.7	TSL:1 MANE Select	c.365C>T	p.Thr122Met	missense	Exon 3 of 5	ENSP00000388336.2	Q16563-2
	SYPL1	ENST00000011473.6	TSL:1	c.419C>T	p.Thr140Met	missense	Exon 4 of 6	ENSP00000011473.2	Q16563-1
	SYPL1	ENST00000706299.1		c.497C>T	p.Thr166Met	missense	Exon 5 of 7	ENSP00000516340.1	A0A994J846

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461496 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727028

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111796

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.63
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.95	L
PhyloP100		0.80
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.053
Sift	Benign	0.31	T
Sift4G	Benign	0.39	T
Polyphen		0.32	B
Vest4		0.23
MutPred		0.45		Loss of catalytic residue at T140 (P = 0.0418)
MVP		0.16
MPC		0.13
ClinPred		0.19	T
GERP RS		1.2
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.013
gMVP		0.58
Mutation Taster		=87/13	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: rs1044673352; hg19: chr7-105738173;