7-150569921-G-A

Variant names:

• chr7-150569921-G-A
• rs752047449
• NM_018326.3:c.20G>A

Variant summary

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

The NM_018326.3(GIMAP4):​c.20G>A​(p.Ser7Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,428,148 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 (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GIMAP4 NM_018326.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.254
• Publications: 0 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: 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=0.09727487).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018326.3. 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
	GIMAP4	NM_018326.3	MANE Select	c.20G>A	p.Ser7Asn	missense	Exon 2 of 3	NP_060796.1	Q9NUV9
	GIMAP4	NM_001363532.2		c.20G>A	p.Ser7Asn	missense	Exon 2 of 3	NP_001350461.1	G5E9W9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIMAP4	ENST00000255945.4	TSL:1 MANE Select	c.20G>A	p.Ser7Asn	missense	Exon 2 of 3	ENSP00000255945.2	Q9NUV9
	GIMAP4	ENST00000461940.5	TSL:2	c.20G>A	p.Ser7Asn	missense	Exon 2 of 3	ENSP00000419545.1	G5E9W9
	GIMAP4	ENST00000851189.1		c.20G>A	p.Ser7Asn	missense	Exon 3 of 4	ENSP00000521248.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1428148 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 711720

African (AFR) AF: 0.00 AC: 0 AN: 32740

American (AMR) AF: 0.00 AC: 0 AN: 44298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25610

East Asian (EAS) AF: 0.00 AC: 0 AN: 38888

South Asian (SAS) AF: 0.00 AC: 0 AN: 85678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1083880

Other (OTH) AF: 0.00 AC: 0 AN: 58964

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.9
DANN	Benign	0.90
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.25
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.070
Sift	Benign	0.045	D
Sift4G	Benign	0.37	T
Polyphen		0.42	B
Vest4		0.13
MutPred		0.19		Loss of sheet (P = 0.0181)
MVP		0.28
MPC		0.056
ClinPred		0.23	T
GERP RS		2.4
Varity_R		0.070
gMVP		0.38
Mutation Taster		=99/1	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: rs752047449; hg19: chr7-150267009;