chr15-43836176-C-T

Variant names:

• chr15-43836176-C-T
• rs377752604
• NM_024908.4:c.568C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024908.4(WDR76):​c.568C>T​(p.Arg190Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000616 in 1,606,614 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000061 (1 hom.)
• Consequence: WDR76 NM_024908.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16300702).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024908.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR76	NM_024908.4	MANE Select	c.568C>T	p.Arg190Cys	missense	Exon 4 of 13	NP_079184.2	Q9H967
	WDR76	NM_001167941.2		c.376C>T	p.Arg126Cys	missense	Exon 4 of 13	NP_001161413.1	A0A0C4DFX7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR76	ENST00000263795.11	TSL:1 MANE Select	c.568C>T	p.Arg190Cys	missense	Exon 4 of 13	ENSP00000263795.6	Q9H967
	WDR76	ENST00000381246.6	TSL:1	c.376C>T	p.Arg126Cys	missense	Exon 4 of 13	ENSP00000370645.2	A0A0C4DFX7
	WDR76	ENST00000965236.1		c.478C>T	p.Arg160Cys	missense	Exon 3 of 12	ENSP00000635295.1

Frequencies

GnomAD3 genomes AF: 0.0000659 AC: 10 AN: 151746 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.0000809 AC: 20 AN: 247264 AF XY: 0.0000523

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.000334

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000612 AC: 89 AN: 1454750 Hom.: 1 Cov.: 30 AF XY: 0.0000567 AC XY: 41 AN XY: 723374

African (AFR) AF: 0.0000901 AC: 3 AN: 33292

American (AMR) AF: 0.000274 AC: 12 AN: 43856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39454

South Asian (SAS) AF: 0.000118 AC: 10 AN: 84396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000523 AC: 58 AN: 1108608

Other (OTH) AF: 0.0000333 AC: 2 AN: 60116

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 151864 Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 5 AN XY: 74196

African (AFR) AF: 0.0000483 AC: 2 AN: 41400

American (AMR) AF: 0.0000658 AC: 1 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10492

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68000

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000213 Hom.: 0

Bravo AF: 0.0000945

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000115 AC: 14

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.16	T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.1
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.32
MVP		0.73
MPC		0.59
ClinPred		0.33	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.35
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs377752604; hg19: chr15-44128374; COSMIC: COSV55479698;