chr1-160881206-G-T

Variant names:

• chr1-160881206-G-T
• rs370631307
• NM_017625.3:c.512C>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_017625.3(ITLN1):​c.512C>A​(p.Thr171Lys) variant causes a missense change. 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. T171M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ITLN1 NM_017625.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.94
• Publications: 4 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.956

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITLN1	NM_017625.3	c.512C>A	p.Thr171Lys	missense_variant	Exon 5 of 8	ENST00000326245.4	NP_060095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITLN1	ENST00000326245.4	c.512C>A	p.Thr171Lys	missense_variant	Exon 5 of 8	1	NM_017625.3	ENSP00000323587.3
ITLN1	ENST00000464077.1	n.446C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
ITLN1	ENST00000487531.1	n.316C>A		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.64	D
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		4.9
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.70		Gain of solvent accessibility (P = 0.0044);
MVP		0.74
MPC		0.62
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.93
gMVP		0.88
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs370631307; hg19: chr1-160850996; COSMIC: COSV58273846;