NM_018326.3:c.20G>C

Variant names:

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

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>C​(p.Ser7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 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. 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. S7N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: GIMAP4 NM_018326.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.099086374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP4	NM_018326.3	c.20G>C	p.Ser7Thr	missense_variant	Exon 2 of 3	ENST00000255945.4	NP_060796.1
GIMAP4	NM_001363532.2	c.20G>C	p.Ser7Thr	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.20G>C	p.Ser7Thr	missense_variant	Exon 2 of 3	1	NM_018326.3	ENSP00000255945.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428148 Hom.: 0 Cov.: 27 AF XY: 0.00000141 AC XY: 1 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: 9.23e-7 AC: 1 AN: 1083880

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.9
DANN	Benign	0.56
DEOGEN2	Benign	0.026	T;.;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.34	T;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.099	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.;.
PhyloP100		0.25
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.11	N;N;N
REVEL	Benign	0.076
Sift	Benign	0.039	D;T;D
Sift4G	Benign	0.31	T;T;T
Polyphen		0.60	P;P;.
Vest4		0.17
MutPred		0.14		Gain of glycosylation at S7 (P = 0.0517);Gain of glycosylation at S7 (P = 0.0517);Gain of glycosylation at S7 (P = 0.0517);
MVP		0.32
MPC		0.060
ClinPred		0.23	T
GERP RS		2.4
Varity_R		0.079
gMVP		0.39
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;