Genetic Variant GIMAP5:p.Ala91Ala (chr7-150742412-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_018384.5(GIMAP5):c.273C>T(p.Ala91Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,613,836 control chromosomes in the GnomAD database, including 86,078 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 12088 hom., cov: 31)

Exomes 𝑓: 0.31 ( 73990 hom. )

Consequence

GIMAP5
NM_018384.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.44

Variant links:

Genes affected

GIMAP5 (HGNC:18005): (GTPase, IMAP family member 5) This gene encodes a protein belonging to the GTP-binding superfamily and to the immuno-associated nucleotide (IAN) subfamily of nucleotide-binding proteins. In humans, the IAN subfamily genes are located in a cluster at 7q36.1. This gene encodes an antiapoptotic protein that functions in T-cell survival. Polymorphisms in this gene are associated with systemic lupus erythematosus. Read-through transcription exists between this gene and the neighboring upstream GIMAP1 (GTPase, IMAP family member 1) gene. [provided by RefSeq, Dec 2010]

GIMAP5 links:

GIMAP1-GIMAP5 (HGNC:51257): (GIMAP1-GIMAP5 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring GIMAP1 (GTPase, IMAP family member 1) and GIMAP5 (GTPase, IMAP family member 5) genes on chromosome 7. Alternative splicing results in multiple readthrough transcript variants, one of which encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jan 2015]

GIMAP1-GIMAP5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP7

Synonymous conserved (PhyloP=-3.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP5	NM_018384.5 link	c.273C>T	p.Ala91Ala	synonymous_variant	Exon 3 of 3	ENST00000358647.5	NP_060854.2	Q96F15-1A0A090N8P9
GIMAP1-GIMAP5	NM_001199577.2 link	c.885C>T	p.Ala295Ala	synonymous_variant	Exon 6 of 6		NP_001186506.1	A0A087WTJ2
GIMAP1-GIMAP5	NM_001303630.2 link	c.501C>T	p.Ala167Ala	synonymous_variant	Exon 5 of 5		NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP5	ENST00000358647.5 link	c.273C>T	p.Ala91Ala	synonymous_variant	Exon 3 of 3	1	NM_018384.5	ENSP00000351473.3		Q96F15-1
GIMAP1-GIMAP5	ENST00000611999.4 link	c.885C>T	p.Ala295Ala	synonymous_variant	Exon 6 of 6	5		ENSP00000477920.1		A0A087WTJ2

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

57934

AN:

151852

Hom.:

12067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.553

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.401

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.348

GnomAD3 exomes

AF:

0.328

AC:

82363

AN:

251238

Hom.:

14359

AF XY:

0.330

AC XY:

44765

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.557

Gnomad AMR exome

AF:

0.228

Gnomad ASJ exome

AF:

0.322

Gnomad EAS exome

AF:

0.268

Gnomad SAS exome

AF:

0.377

Gnomad FIN exome

AF:

0.397

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.314

AC:

458786

AN:

1461866

Hom.:

73990

Cov.:

AF XY:

0.316

AC XY:

229759

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.560

Gnomad4 AMR exome

AF:

0.236

Gnomad4 ASJ exome

AF:

0.325

Gnomad4 EAS exome

AF:

0.276

Gnomad4 SAS exome

AF:

0.377

Gnomad4 FIN exome

AF:

0.392

Gnomad4 NFE exome

AF:

0.302

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.382

AC:

58008

AN:

151970

Hom.:

12088

Cov.:

AF XY:

0.385

AC XY:

28559

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.553

Gnomad4 AMR

AF:

0.285

Gnomad4 ASJ

AF:

0.344

Gnomad4 EAS

AF:

0.284

Gnomad4 SAS

AF:

0.395

Gnomad4 FIN

AF:

0.401

Gnomad4 NFE

AF:

0.308

Gnomad4 OTH

AF:

0.349

Alfa

AF:

0.320

Hom.:

16147

Bravo

AF:

0.377

Asia WGS

AF:

0.356

AC:

1239

AN:

3478

EpiCase

AF:

0.307

EpiControl

AF:

0.298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.9

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over