chr17-54999751-C-G

Variant names:

• chr17-54999751-C-G
• rs1223223320
• NM_178509.6:c.407C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178509.6(STXBP4):​c.407C>G​(p.Thr136Arg) 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 1,461,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: STXBP4 NM_178509.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04806328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP4	NM_178509.6	c.407C>G	p.Thr136Arg	missense_variant	Exon 6 of 18	ENST00000376352.6	NP_848604.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP4	ENST00000376352.6	c.407C>G	p.Thr136Arg	missense_variant	Exon 6 of 18	2	NM_178509.6	ENSP00000365530.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461358 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726996

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.76
DEOGEN2	Benign	0.0082	T;T;T;.
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.75	T;T;T;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.048	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.74	N;N;N;N
REVEL	Benign	0.049
Sift	Benign	0.73	T;T;T;T
Sift4G	Benign	0.60	T;T;T;T
Polyphen		0.037	B;.;B;B
Vest4		0.28
MutPred		0.19		Loss of glycosylation at T136 (P = 0.0346);Loss of glycosylation at T136 (P = 0.0346);Loss of glycosylation at T136 (P = 0.0346);.;
MVP		0.32
MPC		0.18
ClinPred		0.92	D
GERP RS		1.9
Varity_R		0.079
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1223223320; hg19: chr17-53077112;