chr9-124856847-A-G

Position:

• chr9-124856847-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001045476.3(WDR38):​c.734A>G​(p.Glu245Gly) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR38 NM_001045476.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.718

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028514326).
• BP6: Variant 9-124856847-A-G is Benign according to our data. Variant chr9-124856847-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3332822.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR38	NM_001045476.3	c.734A>G	p.Glu245Gly	missense_variant	7/9	ENST00000373574.2	NP_001038941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR38	ENST00000373574.2	c.734A>G	p.Glu245Gly	missense_variant	7/9	1	NM_001045476.3	ENSP00000362677.1
WDR38	ENST00000613760.4	c.734A>G	p.Glu245Gly	missense_variant	7/9	1		ENSP00000483312.1
WDR38	ENST00000618744.4	c.587A>G	p.Glu196Gly	missense_variant	6/8	1		ENSP00000483432.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.80
DANN	Benign	0.53
DEOGEN2	Benign	0.0044	.;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.029	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.2	.;.;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	5.5	.;.;N
REVEL	Benign	0.13
Sift	Benign	1.0	.;.;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.12
MutPred		0.53		Loss of stability (P = 0.0871);.;Loss of stability (P = 0.0871);
MVP		0.12
MPC		0.19
ClinPred		0.062	T
GERP RS		2.5
Varity_R		0.027
gMVP		0.56

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: chr9-127619126;