chr4-106358296-A-G

Position:

• chr4-106358296-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195138.2(GIMD1):​c.541T>C​(p.Tyr181His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000362 in 1,380,804 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 0.0000036 (1 hom.)
• Consequence: GIMD1 NM_001195138.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11359775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIMD1	NM_001195138.2	c.541T>C	p.Tyr181His	missense_variant	3/3	ENST00000638719.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIMD1	ENST00000638719.4	c.541T>C	p.Tyr181His	missense_variant	3/3	5	NM_001195138.2	P1
GIMD1	ENST00000507153.2	c.541T>C	p.Tyr181His	missense_variant	2/2	2		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000362 AC: 5 AN: 1380804 Hom.: 1 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 681330

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: 0.0000254

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000279

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

Jul 09, 2021

The c.541T>C (p.Y181H) alteration is located in exon 2 (coding exon 2) of the GIMD1 gene. This alteration results from a T to C substitution at nucleotide position 541, causing the tyrosine (Y) at amino acid position 181 to be replaced by a histidine (H). 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	0.22
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.65
DEOGEN2	Benign	0.025	T;T
FATHMM_MKL	Benign	0.63	D
MetaRNN	Benign	0.11	T;T
MutationAssessor	Benign	1.9	M;M
PrimateAI	Benign	0.38	T
GERP RS		4.5
Varity_R		0.11
gMVP		0.60

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-107279453;