chr13-20704101-C-G

Variant names:

• chr13-20704101-C-G
• NM_001385224.1:c.100C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385224.1(IL17D):​c.100C>G​(p.Arg34Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000018 in 1,108,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: IL17D NM_001385224.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.940

Genes affected

IL17D (HGNC:5984): (interleukin 17D) The protein encoded by this gene is a cytokine that shares the sequence similarity with IL17. The treatment of endothelial cells with this cytokine has been shown to stimulate the production of other cytokines including IL6, IL8 and CSF2/ GM-CSF. The increased expression of IL8 induced by this cytokine was found to be NF-kappa B-dependent. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24018896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17D	NM_001385224.1	c.100C>G	p.Arg34Gly	missense_variant	Exon 1 of 2	ENST00000682841.1	NP_001372153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17D	ENST00000682841.1	c.100C>G	p.Arg34Gly	missense_variant	Exon 1 of 2		NM_001385224.1	ENSP00000508385.1
IL17D	ENST00000304920.3	c.100C>G	p.Arg34Gly	missense_variant	Exon 2 of 3	1		ENSP00000302924.3
IL17D	ENST00000468605.1	n.22C>G		non_coding_transcript_exon_variant	Exon 1 of 3	3		ENSP00000480610.1
IL17D	ENST00000498088.1	c.*15C>G		downstream_gene_variant		2		ENSP00000479852.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000180 AC: 2 AN: 1108848 Hom.: 0 Cov.: 31 AF XY: 0.00000185 AC XY: 1 AN XY: 541778

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000518

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.100C>G (p.R34G) alteration is located in exon 2 (coding exon 1) of the IL17D gene. This alteration results from a C to G substitution at nucleotide position 100, causing the arginine (R) at amino acid position 34 to be replaced by a glycine (G). 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	Pathogenic	0.64
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.024
Eigen_PC	Benign	-0.029
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.16
Sift	Benign	0.47	T
Sift4G	Benign	0.22	T
Polyphen		0.65	P
Vest4		0.11
MutPred		0.71		Loss of MoRF binding (P = 0.0564);
MVP		0.62
MPC		1.5
ClinPred		0.72	D
GERP RS		2.8
Varity_R		0.21
gMVP		0.46

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.

Other links and lift over

hg19: chr13-21278240;