rs1453668952

Variant names:

• chr9-124853589-C-T
• rs1453668952
• NM_001045476.3:c.58C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-124853589-C-T
• chr9-124853589-C-A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001045476.3(WDR38):​c.58C>T​(p.His20Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000048 in 1,270,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000052 (0 hom.)
• Consequence: WDR38 NM_001045476.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35
• Publications: 0 publications found

Genes affected

WDR38 (HGNC:23745): (WD repeat domain 38) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.949

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001045476.3. 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
	WDR38	NM_001045476.3	MANE Select	c.58C>T	p.His20Tyr	missense	Exon 1 of 9	NP_001038941.1	Q5JTN6
	WDR38	NM_001276374.2		c.58C>T	p.His20Tyr	missense	Exon 1 of 9	NP_001263303.1	A0A087X0D8
	WDR38	NM_001276375.2		c.58C>T	p.His20Tyr	missense	Exon 1 of 9	NP_001263304.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR38	ENST00000373574.2	TSL:1 MANE Select	c.58C>T	p.His20Tyr	missense	Exon 1 of 9	ENSP00000362677.1	Q5JTN6
	WDR38	ENST00000613760.4	TSL:1	c.58C>T	p.His20Tyr	missense	Exon 1 of 9	ENSP00000483312.1	A0A087X0D8
	WDR38	ENST00000618744.4	TSL:1	c.-37C>T		5_prime_UTR	Exon 1 of 8	ENSP00000483432.1	A0A087X0J1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000519 AC: 58 AN: 1117990 Hom.: 0 Cov.: 30 AF XY: 0.0000566 AC XY: 30 AN XY: 530166

African (AFR) AF: 0.00 AC: 0 AN: 24528

American (AMR) AF: 0.00 AC: 0 AN: 9954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14522

East Asian (EAS) AF: 0.00 AC: 0 AN: 29150

South Asian (SAS) AF: 0.00 AC: 0 AN: 21256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4482

European-Non Finnish (NFE) AF: 0.0000611 AC: 57 AN: 932598

Other (OTH) AF: 0.0000223 AC: 1 AN: 44860

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152218 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	-0.014	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		2.4
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0090	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.46
MutPred		0.81		Loss of disorder (P = 0.0433)
MVP		0.70
MPC		0.74
ClinPred		0.98	D
GERP RS		4.5
PromoterAI		0.021	Neutral
Varity_R		0.63
gMVP		0.31
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs1453668952; hg19: chr9-127615868;