chr9-124855716-T-G

Position:

• chr9-124855716-T-G

Variant summary

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

The NM_001045476.3(WDR38):​c.273T>G​(p.Asp91Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,170 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 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: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: WDR38 NM_001045476.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.298

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.273T>G	p.Asp91Glu	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.273T>G	p.Asp91Glu	missense_variant	3/9	1	NM_001045476.3	ENSP00000362677.1
WDR38	ENST00000613760.4	c.273T>G	p.Asp91Glu	missense_variant	3/9	1		ENSP00000483312.1
WDR38	ENST00000618744.4	c.97-81T>G		intron_variant		1		ENSP00000483432.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152170 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: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74334

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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

Oct 04, 2024

The c.273T>G (p.D91E) alteration is located in exon 3 (coding exon 3) of the WDR38 gene. This alteration results from a T to G substitution at nucleotide position 273, causing the aspartic acid (D) at amino acid position 91 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	Uncertain	0.46
BayesDel_addAF	Benign	-0.0091	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	2.5
DANN	Benign	0.60
DEOGEN2	Benign	0.068	.;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.8	.;D
REVEL	Uncertain	0.31
Sift	Benign	0.095	.;T
Sift4G	Benign	0.34	T;T
Polyphen		0.97	.;D
Vest4		0.47
MutPred		0.66		Loss of MoRF binding (P = 0.1075);Loss of MoRF binding (P = 0.1075);
MVP		0.37
MPC		0.50
ClinPred		0.67	D
GERP RS		-0.73
Varity_R		0.081
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1337159924; hg19: chr9-127617995;