7-150742806-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_018384.5(GIMAP5):c.667C>T(p.Leu223Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GIMAP5 NM_018384.5 missense
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 0.834

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]

GIMAP1-GIMAP5 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-150742806-C-T is Pathogenic according to our data. Variant chr7-150742806-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1344845.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.35937855).. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIMAP5	NM_018384.5	c.667C>T	p.Leu223Phe	missense_variant	3/3	ENST00000358647.5
GIMAP1-GIMAP5	NM_001199577.2	c.1279C>T	p.Leu427Phe	missense_variant	6/6
GIMAP1-GIMAP5	NM_001303630.2	c.895C>T	p.Leu299Phe	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIMAP5	ENST00000358647.5	c.667C>T	p.Leu223Phe	missense_variant	3/3	1	NM_018384.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461882 Hom.: 0 Cov.: 72 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.0000299

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Portal hypertension Pathogenic:1

Likely pathogenic, no assertion criteria provided

literature only

Yale Center for Mendelian Genomics, Yale University

May 06, 2021

- -

Portal hypertension, noncirrhotic, 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 03, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	22
Dann	Uncertain	1.0
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.078
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.80	T;.;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.42	T
Sift4G	Uncertain	0.014	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.32
MutPred		0.64		.;Loss of stability (P = 0.0375);Loss of stability (P = 0.0375);
MVP		0.14
MPC		0.18
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.50
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150439894;