NM_018463.4:c.10G>C

Variant names:

• chr12-2812770-G-C
• rs772882740
• NM_018463.4:c.10G>C

Variant summary

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

The NM_018463.4(ITFG2):​c.10G>C​(p.Val4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. V4I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITFG2 NM_018463.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35
• Publications: 0 publications found

Genes affected

ITFG2 (HGNC:30879): (integrin alpha FG-GAP repeat containing 2) Involved in cellular response to amino acid starvation; cellular response to glucose starvation; and negative regulation of TORC1 signaling. Located in lysosomal membrane. Part of KICSTOR complex. [provided by Alliance of Genome Resources, Apr 2022]

ITFG2-AS1 (HGNC:53128): (ITFG2 antisense RNA 1)

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=0.10075602).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018463.4. 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
	ITFG2	NM_018463.4	MANE Select	c.10G>C	p.Val4Leu	missense	Exon 1 of 12	NP_060933.3
	ITFG2	NR_130744.3		n.103G>C		non_coding_transcript_exon	Exon 1 of 14
	ITFG2-AS1	NR_146317.1		n.155C>G		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITFG2	ENST00000228799.7	TSL:1 MANE Select	c.10G>C	p.Val4Leu	missense	Exon 1 of 12	ENSP00000228799.2	Q969R8-1
	ITFG2	ENST00000537851.5	TSL:1	n.10G>C		non_coding_transcript_exon	Exon 1 of 9	ENSP00000445769.1	F5H1D0
	ITFG2	ENST00000917242.1		c.10G>C	p.Val4Leu	missense	Exon 1 of 12	ENSP00000587301.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.27
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.16
Sift	Benign	0.083	T
Sift4G	Benign	0.086	T
Polyphen		0.0090	B
Vest4		0.12
MutPred		0.26		Loss of sheet (P = 0.0228)
MVP		0.27
MPC		0.33
ClinPred		0.47	T
GERP RS		4.6
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.20
gMVP		0.32
Mutation Taster		=89/11	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: rs772882740; hg19: chr12-2921936;