NM_001195138.2:c.544G>A

Variant names:

• chr4-106358293-C-T
• rs7654865
• NM_001195138.2:c.544G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001195138.2(GIMD1):​c.544G>A​(p.Val182Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,525,642 control chromosomes in the GnomAD database, including 23,648 homozygotes. 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: 𝑓 0.15 (1857 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21791 hom.)
• Consequence: GIMD1 NM_001195138.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 18 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032345057).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195138.2. 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
	GIMD1	NM_001195138.2	MANE Select	c.544G>A	p.Val182Ile	missense	Exon 3 of 3	NP_001182067.1	P0DJR0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIMD1	ENST00000638719.4	TSL:5 MANE Select	c.544G>A	p.Val182Ile	missense	Exon 3 of 3	ENSP00000491450.2	P0DJR0
	GIMD1	ENST00000507153.2	TSL:2	c.544G>A	p.Val182Ile	missense	Exon 2 of 2	ENSP00000489975.1	P0DJR0

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23044 AN: 151556 Hom.: 1857 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.141

GnomAD2 exomes AF: 0.163 AC: 21402 AN: 131400 AF XY: 0.170

Gnomad AFR exome AF: 0.0979

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.135

Gnomad FIN exome AF: 0.197

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.173 AC: 238340 AN: 1373968 Hom.: 21791 Cov.: 30 AF XY: 0.175 AC XY: 118988 AN XY: 678040

African (AFR) AF: 0.101 AC: 3162 AN: 31264

American (AMR) AF: 0.119 AC: 4207 AN: 35250

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 2928 AN: 24986

East Asian (EAS) AF: 0.177 AC: 6311 AN: 35592

South Asian (SAS) AF: 0.243 AC: 18956 AN: 78018

European-Finnish (FIN) AF: 0.200 AC: 6765 AN: 33840

Middle Eastern (MID) AF: 0.142 AC: 801 AN: 5636

European-Non Finnish (NFE) AF: 0.173 AC: 185420 AN: 1071840

Other (OTH) AF: 0.170 AC: 9790 AN: 57542

GnomAD4 genome AF: 0.152 AC: 23052 AN: 151674 Hom.: 1857 Cov.: 32 AF XY: 0.154 AC XY: 11392 AN XY: 74112

African (AFR) AF: 0.108 AC: 4452 AN: 41396

American (AMR) AF: 0.118 AC: 1797 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3464

East Asian (EAS) AF: 0.138 AC: 708 AN: 5132

South Asian (SAS) AF: 0.250 AC: 1199 AN: 4804

European-Finnish (FIN) AF: 0.198 AC: 2088 AN: 10530

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11817 AN: 67812

Other (OTH) AF: 0.142 AC: 299 AN: 2112

Alfa AF: 0.163 Hom.: 6658

Bravo AF: 0.142

TwinsUK AF: 0.173 AC: 640

ALSPAC AF: 0.177 AC: 682

ExAC AF: 0.180 AC: 2613

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.9
DANN	Benign	0.74
DEOGEN2	Benign	0.0068	T
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0032	T
MutationAssessor	Benign	0.19	N
PhyloP100		-0.0030
PrimateAI	Benign	0.26	T
GERP RS		0.26
Varity_R		0.022
gMVP		0.066
Mutation Taster		=97/3	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs7654865; hg19: chr4-107279450; COSMIC: COSV72511974;