chr9-124856289-G-A

Position:

• chr9-124856289-G-A

Variant summary

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

The NM_001045476.3(WDR38):​c.455G>A​(p.Ser152Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 2.89

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR38	NM_001045476.3	c.455G>A	p.Ser152Asn	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.455G>A	p.Ser152Asn	missense_variant	5/9	1	NM_001045476.3	ENSP00000362677.1
WDR38	ENST00000613760.4	c.455G>A	p.Ser152Asn	missense_variant	5/9	1		ENSP00000483312.1
WDR38	ENST00000618744.4	c.308G>A	p.Ser103Asn	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

Apr 12, 2024

The c.455G>A (p.S152N) alteration is located in exon 5 (coding exon 5) of the WDR38 gene. This alteration results from a G to A substitution at nucleotide position 455, causing the serine (S) at amino acid position 152 to be replaced by an asparagine (N). 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	Uncertain	0.46
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	.;.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Uncertain	2.9	.;.;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.7	.;.;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.021	.;.;D
Sift4G	Uncertain	0.020	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.52
MutPred		0.51		Loss of disorder (P = 0.0879);.;Loss of disorder (P = 0.0879);
MVP		0.76
MPC		0.61
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.64
gMVP		0.75

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-127618568;