15-43835107-T-C

Position:

• chr15-43835107-T-C

Variant summary

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

The NM_024908.4(WDR76):​c.509T>C​(p.Ile170Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.45

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 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
WDR76	NM_024908.4	c.509T>C	p.Ile170Thr	missense_variant	3/13	ENST00000263795.11	NP_079184.2
WDR76	NM_001167941.2	c.317T>C	p.Ile106Thr	missense_variant	3/13		NP_001161413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR76	ENST00000263795.11	c.509T>C	p.Ile170Thr	missense_variant	3/13	1	NM_024908.4	ENSP00000263795.6
WDR76	ENST00000381246.6	c.317T>C	p.Ile106Thr	missense_variant	3/13	1		ENSP00000370645.2
WDR76	ENST00000452115.1	c.317T>C	p.Ile106Thr	missense_variant	3/7	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2023

The c.509T>C (p.I170T) alteration is located in exon 3 (coding exon 3) of the WDR76 gene. This alteration results from a T to C substitution at nucleotide position 509, causing the isoleucine (I) at amino acid position 170 to be replaced by a threonine (T). 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	0.95
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;T;.
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.87	D;D;T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Uncertain	2.9	M;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.91
MutPred		0.46		Gain of helix (P = 0.0093);.;.;
MVP		0.84
MPC		0.67
ClinPred		0.99	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.71
gMVP		0.75

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: chr15-44127305;