22-31426643-AA-TT

Position:

• chr22-31426643-AA-TT

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The NM_004147.4(DRG1):​c.742_743inv​(p.Asn248Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRG1 NM_004147.4 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 8.72

Genes affected

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 22-31426643-AA-TT is Pathogenic according to our data. Variant chr22-31426643-AA-TT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2664493.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRG1	NM_004147.4	c.742_743inv	p.Asn248Phe	missense_variant	7/9	ENST00000331457.9	NP_004138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRG1	ENST00000331457.9	c.742_743inv	p.Asn248Phe	missense_variant	7/9	1	NM_004147.4	ENSP00000329715	P1
DRG1	ENST00000469673.1	n.131_132inv		non_coding_transcript_exon_variant	1/3	2

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

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Tan-Almurshedi syndrome Pathogenic:2

Likely pathogenic, criteria provided, single submitter	curation	SIB Swiss Institute of Bioinformatics	Mar 03, 2024	This variant is interpreted for Tan-Almurshedi syndrome, autosomal recessive. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in gnomAD (PM2). For recessive disorders, detected in trans with a pathogenic variant (PM3). Located in a mutational hot spot and/or critical and well-established functional domain (PM1). Well-established functional studies show a deleterious effect (PS3-supporting). -
Pathogenic, no assertion criteria provided	literature only	OMIM	Dec 07, 2023	- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-31822629;