4-185294982-A-T

Variant names:

• chr4-185294982-A-T
• rs1288547
• NM_001378034.2:c.1162+6900A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001378034.2(SNX25):​c.1162+6900A>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX25 NM_001378034.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597
• Publications: 3 publications found

Genes affected

SNX25 (HGNC:21883): (sorting nexin 25) Predicted to enable type I transforming growth factor beta receptor binding activity. Involved in negative regulation of pathway-restricted SMAD protein phosphorylation; negative regulation of transforming growth factor beta receptor signaling pathway; and receptor catabolic process. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378034.2. 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
	SNX25	NM_001378034.2	MANE Select	c.1162+6900A>T		intron	N/A	NP_001364963.1	A0A494C0S0
	SNX25	NM_001378032.2		c.1261+6900A>T		intron	N/A	NP_001364961.1
	SNX25	NM_001423234.1		c.1162+6900A>T		intron	N/A	NP_001410163.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX25	ENST00000652585.2	MANE Select	c.1162+6900A>T		intron	N/A	ENSP00000498676.1	A0A494C0S0
	SNX25	ENST00000504273.5	TSL:1	c.670+6900A>T		intron	N/A	ENSP00000426255.1	Q9H3E2-1
	SNX25	ENST00000927314.1		c.1162+6900A>T		intron	N/A	ENSP00000597373.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.70
PhyloP100		0.60

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: rs1288547; hg19: chr4-186216136;