Genetic Variant ITFG1:p.Ser523Tyr (chr16-47162550-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030790.5(ITFG1):c.1568C>A(p.Ser523Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000406 in 1,600,912 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 1 hom. )

Consequence

ITFG1
NM_030790.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70

Variant links:

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 links:

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

ITFG1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.121178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITFG1	NM_030790.5 link	c.1568C>A	p.Ser523Tyr	missense_variant	Exon 15 of 18	ENST00000320640.11	NP_110417.2	Q8TB96
ITFG1	NM_001305002.2 link	c.1229C>A	p.Ser410Tyr	missense_variant	Exon 15 of 18		NP_001291931.1	Q8TB96F5GXC5B4DXC2
ITFG1-AS1	NR_110903.1 link	n.685-1G>T		splice_acceptor_variant, intron_variant	Intron 4 of 4
ITFG1-AS1	NR_110904.1 link	n.520-1G>T		splice_acceptor_variant, intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITFG1	ENST00000320640.11 link	c.1568C>A	p.Ser523Tyr	missense_variant	Exon 15 of 18	1	NM_030790.5	ENSP00000319918.6		Q8TB96

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000489

AC:

AN:

245580

Hom.:

AF XY:

0.0000452

AC XY:

AN XY:

132686

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000803

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.0000442

AC:

AN:

1448876

Hom.:

Cov.:

AF XY:

0.0000527

AC XY:

AN XY:

720632

show subpopulations

Gnomad4 AFR exome

AF:

0.0000606

Gnomad4 AMR exome

AF:

0.0000460

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:

0.0000452

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000660

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1568C>A (p.S523Y) alteration is located in exon 15 (coding exon 15) of the ITFG1 gene. This alteration results from a C to A substitution at nucleotide position 1568, causing the serine (S) at amino acid position 523 to be replaced by a tyrosine (Y). 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

0.097

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

T;.;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.0059

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

L;.;.

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.77

N;N;.

REVEL

Benign

0.022

Sift

Benign

0.033

D;D;.

Sift4G

Uncertain

0.029

D;D;D

Polyphen

0.76

P;P;.

Vest4

0.48

MutPred

0.30

Loss of disorder (P = 0.0127);.;.;

MVP

0.082

MPC

1.4

ClinPred

0.11

GERP RS

4.5

Varity_R

0.066

gMVP

0.47

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over