Variant 16-70659729-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001393494.1(IL34):c.514A>T(p.Met172Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,454,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

IL34
NM_001393494.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

Variant links:

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 links:

Genome browser will be placed here

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/exons	MANE	Protein	UniProt
IL34	NM_001393494.1 linkuse as main transcript	c.514A>T	p.Met172Leu	missense_variant	5/6	ENST00000288098.7	NP_001380423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL34	ENST00000288098.7 linkuse as main transcript	c.514A>T	p.Met172Leu	missense_variant	5/6	1	NM_001393494.1	ENSP00000288098	P2	Q6ZMJ4-1
IL34	ENST00000566361.1 linkuse as main transcript	c.439A>T	p.Met147Leu	missense_variant	5/6	1		ENSP00000463886	A2
IL34	ENST00000429149.6 linkuse as main transcript	c.514A>T	p.Met172Leu	missense_variant	6/7	5		ENSP00000397863	P2	Q6ZMJ4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000424

AC:

AN:

235912

Hom.:

AF XY:

0.00000783

AC XY:

AN XY:

127780

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000950

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1454368

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723014

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:

0.00000451

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.514A>T (p.M172L) alteration is located in exon 6 (coding exon 5) of the IL34 gene. This alteration results from a A to T substitution at nucleotide position 514, causing the methionine (M) at amino acid position 172 to be replaced by a leucine (L). 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

0.38

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.051

T;T;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.74

T;.;T

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.50

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

2.0

M;M;.

MutationTaster

Benign

0.95

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.3

N;N;.

REVEL

Benign

0.20

Sift

Benign

0.082

T;T;.

Sift4G

Benign

0.22

T;T;T

Polyphen

0.52

P;P;.

Vest4

0.64

MutPred

0.30

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;

MVP

0.67

MPC

0.29

ClinPred

0.66

GERP RS

5.1

Varity_R

0.49

gMVP

0.44

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over