9-124856278-C-G

Position:

• chr9-124856278-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001045476.3(WDR38):​c.444C>G​(p.Asp148Glu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR38 NM_001045476.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.144

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2919305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR38	NM_001045476.3	c.444C>G	p.Asp148Glu	missense_variant	5/9	ENST00000373574.2	NP_001038941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR38	ENST00000373574.2	c.444C>G	p.Asp148Glu	missense_variant	5/9	1	NM_001045476.3	ENSP00000362677.1
WDR38	ENST00000613760.4	c.444C>G	p.Asp148Glu	missense_variant	5/9	1		ENSP00000483312.1
WDR38	ENST00000618744.4	c.297C>G	p.Asp99Glu	missense_variant	4/8	1		ENSP00000483432.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Jul 16, 2024

The c.444C>G (p.D148E) alteration is located in exon 5 (coding exon 5) of the WDR38 gene. This alteration results from a C to G substitution at nucleotide position 444, causing the aspartic acid (D) at amino acid position 148 to be replaced by a glutamic acid (E). 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	0.57
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	.;.;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.4	.;.;L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.1	.;.;N
REVEL	Benign	0.15
Sift	Benign	0.10	.;.;T
Sift4G	Benign	0.32	T;T;T
Polyphen		0.97	.;.;D
Vest4		0.36
MutPred		0.47		Gain of disorder (P = 0.1641);.;Gain of disorder (P = 0.1641);
MVP		0.49
MPC		0.45
ClinPred		0.65	D
GERP RS		0.028
Varity_R		0.084
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-127618557;