rs1453668952

Variant names:

• chr9-124853589-C-A
• NM_001045476.3:c.58C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-124853589-C-A
• chr9-124853589-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001045476.3(WDR38):​c.58C>A​(p.His20Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000894 in 1,117,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H20Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.9e-7 (0 hom.)
• Consequence: WDR38 NM_001045476.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.978

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR38	NM_001045476.3	c.58C>A	p.His20Asn	missense_variant	Exon 1 of 9	ENST00000373574.2	NP_001038941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR38	ENST00000373574.2	c.58C>A	p.His20Asn	missense_variant	Exon 1 of 9	1	NM_001045476.3	ENSP00000362677.1
WDR38	ENST00000613760.4	c.58C>A	p.His20Asn	missense_variant	Exon 1 of 9	1		ENSP00000483312.1
WDR38	ENST00000618744	c.-37C>A		5_prime_UTR_variant	Exon 1 of 8	1		ENSP00000483432.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.94e-7 AC: 1 AN: 1117992 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 530168

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000107

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.075	.;T
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Uncertain	0.013	D
MutationAssessor	Uncertain	2.8	.;M
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-6.5	.;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0030	.;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.60
MutPred		0.85		Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);
MVP		0.79
MPC		0.72
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.80
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-127615868;