16-47161754-G-C

Variant names:

• chr16-47161754-G-C
• NM_030790.5:c.1657C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030790.5(ITFG1):​c.1657C>G​(p.Arg553Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ITFG1 NM_030790.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.19

Genes affected

ITFG1 (HGNC:30697): (integrin alpha FG-GAP repeat containing 1) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ITFG1-AS1 (HGNC:51383): (ITFG1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39262176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITFG1	NM_030790.5	c.1657C>G	p.Arg553Gly	missense_variant	Exon 16 of 18	ENST00000320640.11	NP_110417.2
ITFG1	NM_001305002.2	c.1318C>G	p.Arg440Gly	missense_variant	Exon 16 of 18		NP_001291931.1
ITFG1-AS1	NR_110903.1	n.684+164G>C		intron_variant	Intron 4 of 4
ITFG1-AS1	NR_110904.1	n.519+164G>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITFG1	ENST00000320640.11	c.1657C>G	p.Arg553Gly	missense_variant	Exon 16 of 18	1	NM_030790.5	ENSP00000319918.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450760 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 722536

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1657C>G (p.R553G) alteration is located in exon 16 (coding exon 16) of the ITFG1 gene. This alteration results from a C to G substitution at nucleotide position 1657, causing the arginine (R) at amino acid position 553 to be replaced by a glycine (G). 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	0.14
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T;.;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;T;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	-0.14	N;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.3	N;N;.
REVEL	Benign	0.23
Sift	Benign	0.36	T;D;.
Sift4G	Benign	0.31	T;D;T
Polyphen		0.95	P;D;.
Vest4		0.51
MutPred		0.37		Loss of solvent accessibility (P = 0.0044);.;.;
MVP		0.22
MPC		1.4
ClinPred		0.96	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.27
gMVP		0.73

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-47195665;