chr7-106112172-C-T

Variant names:

• chr7-106112172-C-T
• rs201833481
• NM_182715.4:c.37G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_182715.4(SYPL1):​c.37G>A​(p.Glu13Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000816 in 1,545,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00081 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00082 (0 hom.)
• Consequence: SYPL1 NM_182715.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0646013).

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.37G>A	p.Glu13Lys	missense	Exon 1 of 5	NP_874384.1	Q16563-2
	SYPL1	NM_001381910.1		c.91G>A	p.Glu31Lys	missense	Exon 2 of 7	NP_001368839.1	A0A994J846
	SYPL1	NM_001381911.1		c.37G>A	p.Glu13Lys	missense	Exon 1 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.37G>A	p.Glu13Lys	missense	Exon 1 of 5	ENSP00000388336.2	Q16563-2
	SYPL1	ENST00000011473.6	TSL:1	c.91G>A	p.Glu31Lys	missense	Exon 2 of 6	ENSP00000011473.2	Q16563-1
	SYPL1	ENST00000706299.1		c.91G>A	p.Glu31Lys	missense	Exon 2 of 7	ENSP00000516340.1	A0A994J846

Frequencies

GnomAD3 genomes AF: 0.000806 AC: 122 AN: 151428 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000526

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00126

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000866 AC: 199 AN: 229816 AF XY: 0.000806

Gnomad AFR exome AF: 0.0000741

Gnomad AMR exome AF: 0.000418

Gnomad ASJ exome AF: 0.000210

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000887

Gnomad NFE exome AF: 0.00149

Gnomad OTH exome AF: 0.00129

GnomAD4 exome AF: 0.000817 AC: 1138 AN: 1393472 Hom.: 0 Cov.: 35 AF XY: 0.000843 AC XY: 585 AN XY: 694050

African (AFR) AF: 0.0000665 AC: 2 AN: 30092

American (AMR) AF: 0.000416 AC: 17 AN: 40886

Ashkenazi Jewish (ASJ) AF: 0.000211 AC: 5 AN: 23680

East Asian (EAS) AF: 0.00 AC: 0 AN: 34792

South Asian (SAS) AF: 0.00 AC: 0 AN: 80866

European-Finnish (FIN) AF: 0.00109 AC: 56 AN: 51412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5218

European-Non Finnish (NFE) AF: 0.000959 AC: 1027 AN: 1070472

Other (OTH) AF: 0.000553 AC: 31 AN: 56054

GnomAD4 genome AF: 0.000805 AC: 122 AN: 151536 Hom.: 0 Cov.: 32 AF XY: 0.000837 AC XY: 62 AN XY: 74076

African (AFR) AF: 0.0000723 AC: 3 AN: 41480

American (AMR) AF: 0.000525 AC: 8 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00126 AC: 13 AN: 10310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00143 AC: 97 AN: 67782

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.00106 Hom.: 0

Bravo AF: 0.000612

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000876 AC: 106

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	Pathogenic	0.88
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	0.072
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		2.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.13
Sift	Benign	0.032	D
Sift4G	Benign	0.11	T
Polyphen		0.16	B
Vest4		0.62
MVP		0.088
MPC		0.15
ClinPred		0.20	T
GERP RS		4.3
PromoterAI		0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.91
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201833481; hg19: chr7-105752618; COSMIC: COSV50578691; COSMIC: COSV50578691;