chr15-43835080-C-T

Variant names:

• chr15-43835080-C-T
• NM_024908.4:c.482C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024908.4(WDR76):​c.482C>T​(p.Pro161Leu) 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. 13/21 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)
• Consequence: WDR76 NM_024908.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.91

Genes affected

WDR76 (HGNC:25773): (WD repeat domain 76) Enables enzyme binding activity. Involved in cellular response to DNA damage stimulus. Located in heterochromatin; nucleus; and site of DNA damage. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27878338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR76	NM_024908.4	c.482C>T	p.Pro161Leu	missense_variant	Exon 3 of 13	ENST00000263795.11	NP_079184.2
WDR76	NM_001167941.2	c.290C>T	p.Pro97Leu	missense_variant	Exon 3 of 13		NP_001161413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR76	ENST00000263795.11	c.482C>T	p.Pro161Leu	missense_variant	Exon 3 of 13	1	NM_024908.4	ENSP00000263795.6
WDR76	ENST00000381246.6	c.290C>T	p.Pro97Leu	missense_variant	Exon 3 of 13	1		ENSP00000370645.2
WDR76	ENST00000452115.1	c.290C>T	p.Pro97Leu	missense_variant	Exon 3 of 7	5		ENSP00000404665.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.482C>T (p.P161L) alteration is located in exon 3 (coding exon 3) of the WDR76 gene. This alteration results from a C to T substitution at nucleotide position 482, causing the proline (P) at amino acid position 161 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	Benign	0.10
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T;T;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N;N;D
REVEL	Benign	0.16
Sift	Uncertain	0.020	D;D;D
Sift4G	Benign	0.13	T;T;T
Polyphen		0.51	P;.;.
Vest4		0.52
MutPred		0.34		Loss of loop (P = 0.0288);.;.;
MVP		0.59
MPC		0.15
ClinPred		0.94	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.080
gMVP		0.29

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: chr15-44127278;