Variant chr4-106367258-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001195138.2(GIMD1):c.178C>T(p.Arg60Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,535,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

GIMD1
NM_001195138.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23

Variant links:

Genes affected

GIMD1 (HGNC:44141): (GIMAP family P-loop NTPase domain containing 1) Predicted to enable GTP binding activity. [provided by Alliance of Genome Resources, Apr 2022]

GIMD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014093697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIMD1	NM_001195138.2 linkuse as main transcript	c.178C>T	p.Arg60Cys	missense_variant	2/3	ENST00000638719.4	NP_001182067.1	P0DJR0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIMD1	ENST00000638719.4 linkuse as main transcript	c.178C>T	p.Arg60Cys	missense_variant	2/3	5	NM_001195138.2	ENSP00000491450.2		P0DJR0
GIMD1	ENST00000507153.2 linkuse as main transcript	c.178C>T	p.Arg60Cys	missense_variant	1/2	2		ENSP00000489975.1		P0DJR0

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000395

AC:

AN:

134060

Hom.:

AF XY:

0.000370

AC XY:

AN XY:

72978

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000409

Gnomad ASJ exome

AF:

0.00483

Gnomad EAS exome

AF:

0.0000952

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000172

Gnomad OTH exome

AF:

0.000242

GnomAD4 exome

AF:

0.000155

AC:

214

AN:

1383508

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

110

AN XY:

682718

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00508

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000126

Gnomad4 FIN exome

AF:

0.000354

Gnomad4 NFE exome

AF:

0.0000334

Gnomad4 OTH exome

AF:

0.000380

GnomAD4 genome

AF:

0.000171

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000641

Hom.:

Bravo

AF:

0.000162

ExAC

AF:

0.000327

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.178C>T (p.R60C) alteration is located in exon 1 (coding exon 1) of the GIMD1 gene. This alteration results from a C to T substitution at nucleotide position 178, causing the arginine (R) at amino acid position 60 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Benign

0.53

DEOGEN2

Benign

0.014

T;T

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.86

.;D

MetaRNN

Benign

0.014

T;T

MutationAssessor

Uncertain

2.9

M;M

PrimateAI

Benign

0.45

GERP RS

4.1

Varity_R

0.17

gMVP

0.47

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over