Variant 18-56682776-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015285.3(WDR7):c.443T>C(p.Val148Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,558 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

WDR7
NM_015285.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.99

Variant links:

Genes affected

WDR7 (HGNC:13490): (WD repeat domain 7) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD) that may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. The encoded protein forms the beta subunit of rabconnectin-3 and binds directly with Rab3A GDP/GTP exchange protein and indirectly with Rab3A GDP/GTP activating protein; these proteins are regulators of Rab3 small G protein family members involved in control of the calcium-dependant exocytosis of neurotransmitters. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

WDR7 links:

WDR7 (HGNC:):

WDR7 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/exons	MANE	Protein	UniProt
WDR7	NM_015285.3 linkuse as main transcript	c.443T>C	p.Val148Ala	missense_variant	5/28	ENST00000254442.8	NP_056100.2	Q9Y4E6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR7	ENST00000254442.8 linkuse as main transcript	c.443T>C	p.Val148Ala	missense_variant	5/28	1	NM_015285.3	ENSP00000254442.3	Q9Y4E6-1
WDR7	ENST00000357574.7 linkuse as main transcript	c.443T>C	p.Val148Ala	missense_variant	5/27	5		ENSP00000350187.2	Q9Y4E6-2
WDR7	ENST00000593058.1 linkuse as main transcript	c.443T>C	p.Val148Ala	missense_variant	5/5	3		ENSP00000466438.1	K7EMB8
WDR7	ENST00000589935.1 linkuse as main transcript	c.-1+31200T>C		intron_variant		4		ENSP00000467485.1	K7EPQ4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461558

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727074

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 02, 2024

The c.443T>C (p.V148A) alteration is located in exon 5 (coding exon 4) of the WDR7 gene. This alteration results from a T to C substitution at nucleotide position 443, causing the valine (V) at amino acid position 148 to be replaced by an alanine (A). 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

0.75

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

.;T;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.60

D;D;D

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.7

M;M;.

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.5

D;D;.

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

D;D;.

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.98

D;P;.

Vest4

0.70

MutPred

0.49

Loss of stability (P = 0.0402);Loss of stability (P = 0.0402);Loss of stability (P = 0.0402);

MVP

0.15

MPC

0.98

ClinPred

0.98

GERP RS

4.8

Varity_R

0.60

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over