rs757140831

Variant names:

• chr17-54990898-C-A
• rs757140831
• NM_178509.6:c.121C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-54990898-C-A
• chr17-54990898-C-G
• chr17-54990898-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_178509.6(STXBP4):​c.121C>A​(p.Arg41Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,410 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: STXBP4 NM_178509.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03
• Publications: 0 publications found

Genes affected

STXBP4 (HGNC:19694): (syntaxin binding protein 4) Enables syntaxin binding activity. Involved in several processes, including positive regulation of cell cycle G1/S phase transition; positive regulation of keratinocyte proliferation; and protein stabilization. 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 (BayesDel_noAF=-0.13).
• BP7: Synonymous conserved (PhyloP=2.03 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178509.6. 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
	STXBP4	NM_178509.6	MANE Select	c.121C>A	p.Arg41Arg	synonymous	Exon 4 of 18	NP_848604.3	Q6ZWJ1-1
	STXBP4	NM_001398481.1		c.121C>A	p.Arg41Arg	synonymous	Exon 4 of 18	NP_001385410.1
	STXBP4	NM_001398483.1		c.121C>A	p.Arg41Arg	synonymous	Exon 4 of 17	NP_001385412.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP4	ENST00000376352.6	TSL:2 MANE Select	c.121C>A	p.Arg41Arg	synonymous	Exon 4 of 18	ENSP00000365530.2	Q6ZWJ1-1
	STXBP4	ENST00000434978.6	TSL:1	c.121C>A	p.Arg41Arg	synonymous	Exon 4 of 17	ENSP00000391087.2	E7EPP7
	STXBP4	ENST00000398391.6	TSL:1	c.-52+4632C>A		intron	N/A	ENSP00000381427.2	Q6ZWJ1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451410 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 721840

African (AFR) AF: 0.00 AC: 0 AN: 32660

American (AMR) AF: 0.00 AC: 0 AN: 42180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25910

East Asian (EAS) AF: 0.00 AC: 0 AN: 39164

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108230

Other (OTH) AF: 0.00 AC: 0 AN: 59968

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.13
CADD	Benign	10
DANN	Benign	0.66
PhyloP100		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs757140831; hg19: chr17-53068259;