16-70654628-T-G

Position:

• chr16-70654628-T-G

Variant summary

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

The NM_001393494.1(IL34):​c.119T>G​(p.Phe40Cys) 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 benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL34 NM_001393494.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.354

Genes affected

IL34 (HGNC:28529): (interleukin 34) Interleukin-34 is a cytokine that promotes the differentiation and viability of monocytes and macrophages through the colony-stimulating factor-1 receptor (CSF1R; MIM 164770) (Lin et al., 2008 [PubMed 18467591]).[supplied by OMIM, May 2008]

IL34 (HGNC:):

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=0.252783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL34	NM_001393494.1	c.119T>G	p.Phe40Cys	missense_variant	2/6	ENST00000288098.7	NP_001380423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL34	ENST00000288098.7	c.119T>G	p.Phe40Cys	missense_variant	2/6	1	NM_001393494.1	ENSP00000288098.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2024

The c.119T>G (p.F40C) alteration is located in exon 3 (coding exon 2) of the IL34 gene. This alteration results from a T to G substitution at nucleotide position 119, causing the phenylalanine (F) at amino acid position 40 to be replaced by a cysteine (C). 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	Uncertain	0.51
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T;.;T;T
Eigen	Benign	0.0044
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.71	T;T;.;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L;.;L;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.6	D;D;D;.
REVEL	Benign	0.11
Sift	Uncertain	0.013	D;D;D;.
Sift4G	Uncertain	0.013	D;D;D;D
Polyphen		0.98	D;.;D;.
Vest4		0.51
MutPred		0.36		Gain of catalytic residue at L41 (P = 0.0537);Gain of catalytic residue at L41 (P = 0.0537);Gain of catalytic residue at L41 (P = 0.0537);.;
MVP		0.59
MPC		0.29
ClinPred		0.92	D
GERP RS		0.46
Varity_R		0.54
gMVP		0.27

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: chr16-70688531;