chr10-1080100-A-G

Position:

• chr10-1080100-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014023.4(WDR37):​c.325A>G​(p.Thr109Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR37 NM_014023.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35

Genes affected

WDR37 (HGNC:31406): (WD repeat domain 37) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13943797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR37	NM_014023.4	c.325A>G	p.Thr109Ala	missense_variant	4/14	ENST00000263150.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR37	ENST00000263150.9	c.325A>G	p.Thr109Ala	missense_variant	4/14	1	NM_014023.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.325A>G (p.T109A) alteration is located in exon 4 (coding exon 3) of the WDR37 gene. This alteration results from a A to G substitution at nucleotide position 325, causing the threonine (T) at amino acid position 109 to be replaced by an alanine (A). 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	Benign	0.059
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Benign	0.28
DEOGEN2	Benign	0.023	T;.;T;.;T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.060
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.76	.;T;T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.2	L;.;.;.;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.19	N;.;N;.;N;N
REVEL	Benign	0.18
Sift	Benign	0.90	T;.;T;.;T;T
Sift4G	Benign	0.92	T;T;T;.;T;T
Polyphen		0.0010	B;.;B;.;B;.
Vest4		0.095
MutPred		0.23		Loss of phosphorylation at T109 (P = 0.0716);Loss of phosphorylation at T109 (P = 0.0716);Loss of phosphorylation at T109 (P = 0.0716);Loss of phosphorylation at T109 (P = 0.0716);Loss of phosphorylation at T109 (P = 0.0716);.;
MVP		0.19
MPC		0.66
ClinPred		0.17	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.072
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs1292135566; hg19: chr10-1126040;