Variant 1-109004623-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001142551.2(WDR47):c.1223A>G(p.Asn408Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

WDR47
NM_001142551.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92

Variant links:

Genes affected

WDR47 (HGNC:29141): (WD repeat domain 47) Predicted to be located in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

WDR47 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05794236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR47	NM_001142551.2 linkuse as main transcript	c.1223A>G	p.Asn408Ser	missense_variant	6/15	ENST00000369962.8	NP_001136023.1	O94967-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR47	ENST00000369962.8 linkuse as main transcript	c.1223A>G	p.Asn408Ser	missense_variant	6/15	1	NM_001142551.2	ENSP00000358979.3	O94967-1
WDR47	ENST00000400794.7 linkuse as main transcript	c.1247A>G	p.Asn416Ser	missense_variant	6/15	1		ENSP00000383599.3	O94967-4
WDR47	ENST00000369965.8 linkuse as main transcript	c.1226A>G	p.Asn409Ser	missense_variant	6/15	1		ENSP00000358982.4	O94967-3
WDR47	ENST00000361054.7 linkuse as main transcript	c.1139A>G	p.Asn380Ser	missense_variant	5/14	5		ENSP00000354339.3	O94967-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251230

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135802

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:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461464

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727048

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:

0.0000187

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 22, 2024

The c.1247A>G (p.N416S) alteration is located in exon 6 (coding exon 5) of the WDR47 gene. This alteration results from a A to G substitution at nucleotide position 1247, causing the asparagine (N) at amino acid position 416 to be replaced by a serine (S). 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

Benign

0.075

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.023

.;T;.;.;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.86

D;D;D;D;D

M_CAP

Benign

0.0038

MetaRNN

Benign

0.058

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L;.;.;.

PrimateAI

Uncertain

0.48

PROVEAN

Benign

0.39

N;N;N;N;N

REVEL

Benign

0.094

Sift

Benign

0.89

T;T;T;T;T

Sift4G

Benign

0.79

T;T;T;T;T

Polyphen

0.0

.;B;B;B;.

Vest4

0.23

MutPred

0.14

.;Gain of phosphorylation at N408 (P = 0.0086);.;.;.;

MVP

0.082

MPC

0.45

ClinPred

0.18

GERP RS

5.5

Varity_R

0.028

gMVP

0.043

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