NM_030790.5:c.1562G>T

Variant names:

• chr16-47162556-C-A
• rs758393141
• NM_030790.5:c.1562G>T

Variant summary

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

The NM_030790.5(ITFG1):​c.1562G>T​(p.Arg521Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,932 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R521H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ITFG1 NM_030790.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.93
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030790.5. 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
	ITFG1	NM_030790.5	MANE Select	c.1562G>T	p.Arg521Leu	missense	Exon 15 of 18	NP_110417.2
	ITFG1	NM_001305002.2		c.1223G>T	p.Arg408Leu	missense	Exon 15 of 18	NP_001291931.1	F5GXC5
	ITFG1-AS1	NR_110903.1		n.690C>A		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITFG1	ENST00000320640.11	TSL:1 MANE Select	c.1562G>T	p.Arg521Leu	missense	Exon 15 of 18	ENSP00000319918.6	Q8TB96
	ITFG1	ENST00000868205.1		c.1673G>T	p.Arg558Leu	missense	Exon 16 of 19	ENSP00000538264.1
	ITFG1	ENST00000868207.1		c.1562G>T	p.Arg521Leu	missense	Exon 15 of 19	ENSP00000538266.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449932 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 721132

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33052

American (AMR) AF: 0.00 AC: 0 AN: 43742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25802

East Asian (EAS) AF: 0.00 AC: 0 AN: 39236

South Asian (SAS) AF: 0.00 AC: 0 AN: 83782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1105752

Other (OTH) AF: 0.00 AC: 0 AN: 59830

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.4	L
PhyloP100		6.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.92	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.027	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.91
MutPred		0.44		Loss of disorder (P = 0.037)
MVP		0.35
MPC		1.2
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.28
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs758393141; hg19: chr16-47196467;