Genetic Variant NM_000572.3:c.513C>A (chr1-206768660-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_000572.3(IL10):c.513C>A(p.Tyr171*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y171Y) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IL10
NM_000572.3 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.890

Variant links:

Genes affected

IL10 (HGNC:5962): (interleukin 10) The protein encoded by this gene is a cytokine produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. Mutations in this gene are associated with an increased susceptibility to HIV-1 infection and rheumatoid arthritis. [provided by RefSeq, May 2020]

IL10 links:

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ACMG classification

Classification made for transcript

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
IL10	NM_000572.3 link	c.513C>A	p.Tyr171*	stop_gained	Exon 5 of 5	ENST00000423557.1	NP_000563.1	P22301Q6FGW4
IL10	NM_001382624.1 link	c.258C>A	p.Tyr86*	stop_gained	Exon 3 of 3		NP_001369553.1
IL10	NR_168466.1 link	n.810C>A		non_coding_transcript_exon_variant	Exon 6 of 6
IL10	NR_168467.1 link	n.340C>A		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL10	ENST00000423557.1 link	c.513C>A	p.Tyr171*	stop_gained	Exon 5 of 5	1	NM_000572.3	ENSP00000412237.1		P22301

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.06e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.50

BayesDel_noAF

Pathogenic

0.48

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Benign

0.72

Vest4

0.90

GERP RS

2.0

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over