rs142355489

Variant names:

• chr7-150569935-C-G
• rs142355489
• NM_018326.3:c.34C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-150569935-C-G
• chr7-150569935-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018326.3(GIMAP4):​c.34C>G​(p.Pro12Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,605,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P12S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: GIMAP4 NM_018326.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.987
• Publications: 2 publications found

Genes affected

GIMAP4 (HGNC:21872): (GTPase, IMAP family member 4) This gene encodes a protein belonging to the GTP-binding superfamily and to the immuno-associated nucleotide (IAN) subfamily of nucleotide-binding proteins. The encoded protein of this gene may be negatively regulated by T-cell acute lymphocytic leukemia 1 (TAL1). In humans, the IAN subfamily genes are located in a cluster at 7q36.1. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04439023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP4	NM_018326.3	c.34C>G	p.Pro12Ala	missense_variant	Exon 2 of 3	ENST00000255945.4	NP_060796.1
GIMAP4	NM_001363532.2	c.34C>G	p.Pro12Ala	missense_variant	Exon 2 of 3		NP_001350461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP4	ENST00000255945.4	c.34C>G	p.Pro12Ala	missense_variant	Exon 2 of 3	1	NM_018326.3	ENSP00000255945.2

Frequencies

GnomAD3 genomes AF: 0.0000725 AC: 11 AN: 151758 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.000483

GnomAD2 exomes AF: 0.0000518 AC: 13 AN: 251046 AF XY: 0.0000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000113 AC: 164 AN: 1453770 Hom.: 0 Cov.: 28 AF XY: 0.000102 AC XY: 74 AN XY: 723692

African (AFR) AF: 0.0000300 AC: 1 AN: 33302

American (AMR) AF: 0.0000671 AC: 3 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86094

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.000135 AC: 149 AN: 1104658

Other (OTH) AF: 0.000166 AC: 10 AN: 60128

GnomAD4 genome AF: 0.0000725 AC: 11 AN: 151758 Hom.: 0 Cov.: 30 AF XY: 0.0000540 AC XY: 4 AN XY: 74090

African (AFR) AF: 0.0000242 AC: 1 AN: 41274

American (AMR) AF: 0.000328 AC: 5 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67928

Other (OTH) AF: 0.000483 AC: 1 AN: 2072

Alfa AF: 0.000127 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.34C>G (p.P12A) alteration is located in exon 2 (coding exon 1) of the GIMAP4 gene. This alteration results from a C to G substitution at nucleotide position 34, causing the proline (P) at amino acid position 12 to be replaced by an alanine (A). 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	0.071
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.12
DANN	Benign	0.48
DEOGEN2	Benign	0.034	T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.39	T;T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.044	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.
PhyloP100		-0.99
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.79	N;N;N
REVEL	Benign	0.024
Sift	Benign	0.54	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.12
MVP		0.13
MPC		0.057
ClinPred		0.087	T
GERP RS		-0.96
Varity_R		0.024
gMVP		0.24
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs142355489; hg19: chr7-150267023;