9-124855647-C-A

Position:

• chr9-124855647-C-A

Variant summary

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

The NM_001045476.3(WDR38):​c.204C>A​(p.Phe68Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR38 NM_001045476.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.698

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

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=0.2406492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR38	NM_001045476.3	c.204C>A	p.Phe68Leu	missense_variant	3/9	ENST00000373574.2	NP_001038941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR38	ENST00000373574.2	c.204C>A	p.Phe68Leu	missense_variant	3/9	1	NM_001045476.3	ENSP00000362677.1
WDR38	ENST00000613760.4	c.204C>A	p.Phe68Leu	missense_variant	3/9	1		ENSP00000483312.1
WDR38	ENST00000618744.4	c.97-150C>A		intron_variant		1		ENSP00000483432.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Mar 06, 2023

The c.204C>A (p.F68L) alteration is located in exon 3 (coding exon 3) of the WDR38 gene. This alteration results from a C to A substitution at nucleotide position 204, causing the phenylalanine (F) at amino acid position 68 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	Pathogenic	0.92
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0083	.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.31	.;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.71	.;N
REVEL	Benign	0.032
Sift	Benign	0.078	.;T
Sift4G	Benign	1.0	T;T
Polyphen		0.15	.;B
Vest4		0.48
MutPred		0.47		Loss of methylation at K67 (P = 0.0355);Loss of methylation at K67 (P = 0.0355);
MVP		0.54
MPC		0.24
ClinPred		0.22	T
GERP RS		2.5
Varity_R		0.071
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1829032173; hg19: chr9-127617926;