chr22-31420261-C-T

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_004147.4(DRG1):​c.418C>T​(p.Arg140*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DRG1
NM_004147.4 stop_gained

Scores

2
4
1

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 4.53
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 22-31420261-C-T is Pathogenic according to our data. Variant chr22-31420261-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2664495.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DRG1NM_004147.4 linkc.418C>T p.Arg140* stop_gained 5/9 ENST00000331457.9 NP_004138.1 Q9Y295

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DRG1ENST00000331457.9 linkc.418C>T p.Arg140* stop_gained 5/91 NM_004147.4 ENSP00000329715.4 Q9Y295
DRG1ENST00000416465.5 linkn.*50C>T non_coding_transcript_exon_variant 4/65 ENSP00000408091.1 F8WEE0
DRG1ENST00000433341.5 linkn.485C>T non_coding_transcript_exon_variant 5/73
DRG1ENST00000416465.5 linkn.*50C>T 3_prime_UTR_variant 4/65 ENSP00000408091.1 F8WEE0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461238
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726832
show subpopulations
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Tan-Almurshedi syndrome Pathogenic:2
Likely pathogenic, criteria provided, single submittercurationSIB Swiss Institute of BioinformaticsMar 03, 2024This 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). Predicted nullvariant in a gene where LOF is a known mechanism of disease (PVS1-strong). -
Pathogenic, no assertion criteria providedliterature onlyOMIMDec 07, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.60
D
BayesDel_noAF
Pathogenic
0.62
CADD
Pathogenic
37
DANN
Uncertain
1.0
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.94
D
Vest4
0.92
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1459583728; hg19: chr22-31816247; API