rs770568145

Variant names:

• chr2-48595280-T-A
• rs770568145
• NM_006873.4:c.2186T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-48595280-T-A
• chr2-48595280-T-C
• chr2-48595280-T-G

Variant summary

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

The NM_006873.4(STON1):​c.2186T>A​(p.Ile729Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I729T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STON1 NM_006873.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• Publications: 1 publications found

Genes affected

STON1 (HGNC:17003): (stonin 1) Endocytosis of cell surface proteins is mediated by a complex molecular machinery that assembles on the inner surface of the plasma membrane. This gene encodes one of two human homologs of the Drosophila melanogaster stoned B protein. This protein is related to components of the endocytic machinery and exhibits a modular structure consisting of an N-terminal proline-rich domain, a central region of homology specific to the human stoned B-like proteins, and a C-terminal region homologous to the mu subunits of adaptor protein (AP) complexes. Read-through transcription of this gene into the neighboring downstream gene, which encodes TFIIA-alpha/beta-like factor, generates a transcript (SALF), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

STON1-GTF2A1L (HGNC:30651): (STON1-GTF2A1L readthrough) STON1-GTF2A1L mRNAs are infrequent but naturally occurring read-through products of the neighboring STON1 and GTF2A1L genes. These transcripts encode fusion proteins composed of the vast majority of each of the individual elements, stonin 1 and general transcription factor IIA, 1-like. Alternative splicing results in multiple transcript variants. The significance of these read-through variants and the function of the resulting protein products have not yet been determined. [provided by RefSeq, Oct 2010]

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=0.069155246).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006873.4. 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
	STON1	NM_006873.4	MANE Select	c.2186T>A	p.Ile729Asn	missense	Exon 4 of 4	NP_006864.2
	STON1	NM_001198595.2		c.2186T>A	p.Ile729Asn	missense	Exon 5 of 5	NP_001185524.1	Q9Y6Q2-1
	STON1-GTF2A1L	NM_172311.3		c.2133+3425T>A		intron	N/A	NP_758515.1	Q53S48

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STON1	ENST00000404752.6	TSL:1 MANE Select	c.2186T>A	p.Ile729Asn	missense	Exon 4 of 4	ENSP00000385273.1	Q9Y6Q2-1
	STON1	ENST00000406226.1	TSL:1	c.2186T>A	p.Ile729Asn	missense	Exon 5 of 5	ENSP00000384615.1	Q9Y6Q2-1
	STON1-GTF2A1L	ENST00000394754.5	TSL:1	c.2133+3425T>A		intron	N/A	ENSP00000378236.1	Q53S48

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		2.4
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.047
Sift	Benign	0.037	D
Sift4G	Uncertain	0.057	T
Polyphen		0.022	B
Vest4		0.18
MutPred		0.14		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.41
ClinPred		0.32	T
GERP RS		3.8
Varity_R		0.10
gMVP		0.12
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs770568145; hg19: chr2-48822419;