16-47155748-C-A

Variant names:

• chr16-47155748-C-A
• rs1964692917
• NM_030790.5:c.1810G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030790.5(ITFG1):​c.1810G>T​(p.Ala604Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000659 in 151,820 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: ITFG1 NM_030790.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.48

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITFG1	NM_030790.5	c.1810G>T	p.Ala604Ser	missense_variant	Exon 18 of 18	ENST00000320640.11	NP_110417.2
ITFG1	NM_001305002.2	c.*20G>T		3_prime_UTR_variant	Exon 18 of 18		NP_001291931.1
ITFG1-AS1	NR_110903.1	n.593-1807C>A		intron_variant	Intron 2 of 4
ITFG1-AS1	NR_110904.1	n.428-1807C>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITFG1	ENST00000320640.11	c.1810G>T	p.Ala604Ser	missense_variant	Exon 18 of 18	1	NM_030790.5	ENSP00000319918.6

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151820 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151820 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74122

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1810G>T (p.A604S) alteration is located in exon 18 (coding exon 18) of the ITFG1 gene. This alteration results from a G to T substitution at nucleotide position 1810, causing the alanine (A) at amino acid position 604 to be replaced by a serine (S). 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	0.32
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.0094	T
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.9	N;.
REVEL	Benign	0.27
Sift	Benign	0.24	T;.
Sift4G	Benign	0.25	T;T
Polyphen		1.0	D;.
Vest4		0.47
MutPred		0.38		Gain of phosphorylation at A604 (P = 0.0073);.;
MVP		0.27
MPC		1.1
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.27
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs1964692917; hg19: chr16-47189659;