1-160880659-G-T

Variant names:

• chr1-160880659-G-T
• rs147618489
• NM_017625.3:c.614C>A

Variant summary

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

The NM_017625.3(ITLN1):​c.614C>A​(p.Pro205Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. P205L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITLN1 NM_017625.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 0 publications found

Genes affected

ITLN1 (HGNC:18259): (intelectin 1) Enables calcium ion binding activity; identical protein binding activity; and oligosaccharide binding activity. Involved in positive regulation of glucose import; positive regulation of protein phosphorylation; and protein homotrimerization. Located in extracellular exosome. Part of receptor 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, 0.788

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITLN1	NM_017625.3	c.614C>A	p.Pro205Gln	missense_variant	Exon 6 of 8	ENST00000326245.4	NP_060095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITLN1	ENST00000326245.4	c.614C>A	p.Pro205Gln	missense_variant	Exon 6 of 8	1	NM_017625.3	ENSP00000323587.3
ITLN1	ENST00000487531.1	n.418C>A		non_coding_transcript_exon_variant	Exon 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.62	D
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.012
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0044	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		1.8
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.58
MutPred		0.53		Gain of catalytic residue at P205 (P = 0.0067);
MVP		0.39
MPC		0.53
ClinPred		1.0	D
GERP RS		3.3
Varity_R		0.33
gMVP		0.90
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs147618489; hg19: chr1-160850449;