22-31504373-C-T

Variant names:

• chr22-31504373-C-T
• rs5749286
• NM_001007467.3:c.-30-3882C>T

Variant summary

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

The NM_001007467.3(SFI1):​c.-30-3882C>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: 31)
• Consequence: SFI1 NM_001007467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 17 publications found

Genes affected

SFI1 (HGNC:29064): (SFI1 centrin binding protein) Enables phosphatase binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

DRG1 (HGNC:3029): (developmentally regulated GTP binding protein 1) Enables several functions, including GTPase activity; identical protein binding activity; and potassium ion binding activity. Involved in positive regulation of microtubule polymerization and regulation of mitotic spindle assembly. Located in cytosol and nuclear body. Part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

DRG1 Gene-Disease associations (from GenCC):

• Tan-Almurshedi syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007467.3. 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
	SFI1	NM_001007467.3	MANE Select	c.-30-3882C>T		intron	N/A	NP_001007468.1	A8K8P3-1
	SFI1	NM_014775.4		c.-30-3882C>T		intron	N/A	NP_055590.2	A8K8P3-2
	SFI1	NM_001258325.1		c.-30-3882C>T		intron	N/A	NP_001245254.1	A8K8P3-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFI1	ENST00000400288.7	TSL:2 MANE Select	c.-30-3882C>T		intron	N/A	ENSP00000383145.2	A8K8P3-1
	SFI1	ENST00000432498.5	TSL:1	c.-30-3882C>T		intron	N/A	ENSP00000402679.1	A8K8P3-2
	SFI1	ENST00000400289.5	TSL:1	c.-26-3886C>T		intron	N/A	ENSP00000383146.1	A8K8P3-3

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 720

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.74
PhyloP100		-1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs5749286; hg19: chr22-31900359;