12-2817248-C-T

Variant names:

• chr12-2817248-C-T
• NM_018463.4:c.122C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018463.4(ITFG2):​c.122C>T​(p.Thr41Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITFG2 NM_018463.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.805

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.122C>T	p.Thr41Ile	missense	Exon 2 of 12	NP_060933.3
	ITFG2	NR_130744.3		n.215C>T		non_coding_transcript_exon	Exon 2 of 14
	ITFG2	NR_147202.2		n.215C>T		non_coding_transcript_exon	Exon 2 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITFG2	ENST00000228799.7	TSL:1 MANE Select	c.122C>T	p.Thr41Ile	missense	Exon 2 of 12	ENSP00000228799.2	Q969R8-1
	ITFG2	ENST00000537851.5	TSL:1	n.97-2838C>T		intron	N/A	ENSP00000445769.1	F5H1D0
	ITFG2	ENST00000917242.1		c.122C>T	p.Thr41Ile	missense	Exon 2 of 12	ENSP00000587301.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.28
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Benign	0.86
DEOGEN2	Benign	0.028	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.0
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.82	N
REVEL	Uncertain	0.29
Sift	Benign	0.077	T
Sift4G	Benign	0.35	T
Polyphen		1.0	D
Vest4		0.86
MutPred		0.45		Gain of catalytic residue at V45 (P = 8e-04)
MVP		0.76
MPC		1.1
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.23
gMVP		0.59
Mutation Taster		=227/73	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

hg19: chr12-2926414;