4-106367300-A-G

Position:

• chr4-106367300-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001195138.2(GIMD1):​c.136T>C​(p.Cys46Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,383,758 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: GIMD1 NM_001195138.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.170

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

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=0.05599001).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIMD1	NM_001195138.2	c.136T>C	p.Cys46Arg	missense_variant	2/3	ENST00000638719.4	NP_001182067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIMD1	ENST00000638719.4	c.136T>C	p.Cys46Arg	missense_variant	2/3	5	NM_001195138.2	ENSP00000491450.2
GIMD1	ENST00000507153.2	c.136T>C	p.Cys46Arg	missense_variant	1/2	2		ENSP00000489975.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000746 AC: 1 AN: 134028 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72966

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000181 AC: 25 AN: 1383758 Hom.: 0 Cov.: 32 AF XY: 0.0000190 AC XY: 13 AN XY: 682824

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: 0.0000232

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.136T>C (p.C46R) alteration is located in exon 1 (coding exon 1) of the GIMD1 gene. This alteration results from a T to C substitution at nucleotide position 136, causing the cysteine (C) at amino acid position 46 to be replaced by an arginine (R). 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	0.077
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.81
DANN	Benign	0.29
DEOGEN2	Benign	0.0051	T;T
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.27	.;T
MetaRNN	Benign	0.056	T;T
MutationAssessor	Benign	0.20	N;N
PrimateAI	Benign	0.27	T
GERP RS		2.3
Varity_R		0.23
gMVP		0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs963071670; hg19: chr4-107288457;