rs678084

Positions:

• chr15-43828361-T-A
• chr15-43828361-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000263795.11(WDR76):​c.457T>A​(p.Ser153Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S153A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WDR76 ENST00000263795.11 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09707114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR76	NM_024908.4	c.457T>A	p.Ser153Thr	missense_variant	2/13	ENST00000263795.11	NP_079184.2
WDR76	NM_001167941.2	c.265T>A	p.Ser89Thr	missense_variant	2/13		NP_001161413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR76	ENST00000263795.11	c.457T>A	p.Ser153Thr	missense_variant	2/13	1	NM_024908.4	ENSP00000263795	P1
WDR76	ENST00000381246.6	c.265T>A	p.Ser89Thr	missense_variant	2/13	1		ENSP00000370645
WDR76	ENST00000452115.1	c.265T>A	p.Ser89Thr	missense_variant	2/7	5		ENSP00000404665

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000414 AC: 1 AN: 241754 Hom.: 0 AF XY: 0.00000765 AC XY: 1 AN XY: 130692

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: 0.00000910

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000207 AC: 3 AN: 1451228 Hom.: 0 Cov.: 47 AF XY: 0.00000278 AC XY: 2 AN XY: 720652

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: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.0089	T;T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.27	T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.097	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.69	N;.;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.59	N;N;N
REVEL	Benign	0.037
Sift	Benign	0.18	T;T;D
Sift4G	Benign	0.17	T;T;T
Polyphen		0.0030	B;.;.
Vest4		0.050
MutPred		0.22		Gain of glycosylation at S153 (P = 0.0593);.;.;
MVP		0.48
MPC		0.12
ClinPred		0.060	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.041
gMVP		0.16

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

Other links and lift over

dbSNP: rs678084; hg19: chr15-44120559;