chrX-49190868-G-A

Variant names:

• chrX-49190868-G-A
• rs3817678
• ENST00000479808.5:c.*569C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000479808.5(SYP):​c.*569C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 114,473 control chromosomes in the GnomAD database, including 12,573 homozygotes. There are 17,002 hemizygotes in GnomAD. 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: 𝑓 0.51 (12007 hom., 16351 hem., cov: 23)
  • Exomes 𝑓: 0.57 (566 hom. 651 hem.)
• Consequence: SYP ENST00000479808.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253
• Publications: 5 publications found

Genes affected

SYP (HGNC:11506): (synaptophysin) This gene encodes an integral membrane protein of small synaptic vesicles in brain and endocrine cells. The protein also binds cholesterol and is thought to direct targeting of vesicle-associated membrane protein 2 (synaptobrevin) to intracellular compartments. Mutations in this gene are associated with an X-linked form of cognitive disability. [provided by RefSeq, Jul 2017]

SYP Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 96

  Inheritance: XL Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Illumina, Ambry Genetics
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000479808.5. 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
	SYP	NM_003179.3	MANE Select	c.*4+565C>T		intron	N/A	NP_003170.1	P08247-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYP	ENST00000479808.5	TSL:1	c.*569C>T		3_prime_UTR	Exon 6 of 6	ENSP00000418169.1	P08247-1
	SYP	ENST00000263233.9	TSL:1 MANE Select	c.*4+565C>T		intron	N/A	ENSP00000263233.4	P08247-1
	SYP	ENST00000920145.1		c.*569C>T		3_prime_UTR	Exon 6 of 6	ENSP00000590204.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 56662 AN: 110109 Hom.: 12013 Cov.: 23

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.547

GnomAD4 exome AF: 0.572 AC: 2465 AN: 4312 Hom.: 566 Cov.: 0 AF XY: 0.597 AC XY: 651 AN XY: 1090

African (AFR) AF: 0.157 AC: 8 AN: 51

American (AMR) AF: 0.368 AC: 286 AN: 778

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 16 AN: 20

East Asian (EAS) AF: 0.266 AC: 41 AN: 154

South Asian (SAS) AF: 0.636 AC: 525 AN: 826

European-Finnish (FIN) AF: 0.586 AC: 34 AN: 58

Middle Eastern (MID) AF: 0.667 AC: 2 AN: 3

European-Non Finnish (NFE) AF: 0.643 AC: 1466 AN: 2281

Other (OTH) AF: 0.617 AC: 87 AN: 141

GnomAD4 genome AF: 0.514 AC: 56656 AN: 110161 Hom.: 12007 Cov.: 23 AF XY: 0.504 AC XY: 16351 AN XY: 32463

African (AFR) AF: 0.241 AC: 7352 AN: 30448

American (AMR) AF: 0.425 AC: 4435 AN: 10424

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2032 AN: 2622

East Asian (EAS) AF: 0.339 AC: 1181 AN: 3480

South Asian (SAS) AF: 0.625 AC: 1626 AN: 2602

European-Finnish (FIN) AF: 0.608 AC: 3468 AN: 5701

Middle Eastern (MID) AF: 0.654 AC: 138 AN: 211

European-Non Finnish (NFE) AF: 0.670 AC: 35198 AN: 52511

Other (OTH) AF: 0.550 AC: 823 AN: 1496

Alfa AF: 0.581 Hom.: 5752

Bravo AF: 0.485

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.4
PhyloP100		0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3817678;

hg19: chrX-49047325;