Genetic Variant GIMD1:p.Val182Leu (chr4-106358293-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001195138.2(GIMD1):c.544G>C(p.Val182Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,378,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict 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)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

GIMD1
NM_001195138.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00300

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

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 (MetaRNN=0.067414135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMD1	NM_001195138.2 link	c.544G>C	p.Val182Leu	missense_variant	Exon 3 of 3	ENST00000638719.4	NP_001182067.1	P0DJR0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMD1	ENST00000638719.4 link	c.544G>C	p.Val182Leu	missense_variant	Exon 3 of 3	5	NM_001195138.2	ENSP00000491450.2		P0DJR0
GIMD1	ENST00000507153.2 link	c.544G>C	p.Val182Leu	missense_variant	Exon 2 of 2	2		ENSP00000489975.1		P0DJR0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1378994

Hom.:

Cov.:

AF XY:

0.00000294

AC XY:

AN XY:

680400

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31332

American (AMR)

AF:

0.00

AC:

AN:

35350

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25032

East Asian (EAS)

AF:

0.00

AC:

AN:

35628

South Asian (SAS)

AF:

0.00

AC:

AN:

78272

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

9.29e-7

AC:

AN:

1076200

Other (OTH)

AF:

0.0000173

AC:

AN:

57674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.8

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.0077

T;T

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.64

.;T

MetaRNN

Benign

0.067

T;T

MutationAssessor

Benign

1.6

L;L

PhyloP100

-0.0030

PrimateAI

Benign

0.27

GERP RS

0.26

Varity_R

0.044

gMVP

0.18

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over