chr7-150737602-G-C

Variant names:

• chr7-150737602-G-C
• rs193233179
• ENST00000611999.4:c.500G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001199577.2(GIMAP1-GIMAP5):​c.500G>C​(p.Arg167Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R167H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: GIMAP1-GIMAP5 NM_001199577.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 0 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• portal hypertension, noncirrhotic, 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07553935).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199577.2. 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
	GIMAP5	NM_018384.5	MANE Select	c.-113G>C		5_prime_UTR	Exon 1 of 3	NP_060854.2
	GIMAP1-GIMAP5	NM_001199577.2		c.500G>C	p.Arg167Pro	missense	Exon 4 of 6	NP_001186506.1	A0A087WTJ2
	GIMAP1-GIMAP5	NM_001303630.2		c.116G>C	p.Arg39Pro	missense	Exon 3 of 5	NP_001290559.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIMAP1-GIMAP5	ENST00000611999.4	TSL:5	c.500G>C	p.Arg167Pro	missense	Exon 4 of 6	ENSP00000477920.1	A0A087WTJ2
	GIMAP5	ENST00000358647.5	TSL:1 MANE Select	c.-113G>C		5_prime_UTR	Exon 1 of 3	ENSP00000351473.3	Q96F15-1
	GIMAP5	ENST00000498181.6	TSL:4	c.-113G>C		5_prime_UTR	Exon 2 of 4	ENSP00000487840.2	Q96F15-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383358 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 682580

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078844

Other (OTH) AF: 0.00 AC: 0 AN: 57900

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	1.6
DANN	Benign	0.72
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.076	T
PhyloP100		-1.6
PrimateAI	Benign	0.32	T
Sift4G	Benign	0.16	T
Vest4		0.17
MVP		0.18
GERP RS		-3.0
PromoterAI		-0.15	Neutral
gMVP		0.94
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs193233179; hg19: chr7-150434690;