chr5-37605234-T-C

Position:

• chr5-37605234-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018034.4(WDR70):​c.1088T>C​(p.Leu363Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: WDR70 NM_018034.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67

Genes affected

WDR70 (HGNC:25495): (WD repeat domain 70) Enables enzyme binding activity. Predicted to be involved in regulation of DNA double-strand break processing and regulation of histone H2B conserved C-terminal lysine ubiquitination. Predicted to be active in nucleus and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27108368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR70	NM_018034.4	c.1088T>C	p.Leu363Ser	missense_variant	10/18	ENST00000265107.9	NP_060504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR70	ENST00000265107.9	c.1088T>C	p.Leu363Ser	missense_variant	10/18	1	NM_018034.4	ENSP00000265107	P1
WDR70	ENST00000504564.1	c.1088T>C	p.Leu363Ser	missense_variant	10/12	1		ENSP00000425841
WDR70	ENST00000510699.1	n.445T>C		non_coding_transcript_exon_variant	4/7	5
WDR70	ENST00000511906.5	n.1102T>C		non_coding_transcript_exon_variant	9/15	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Jan 29, 2024

The c.1088T>C (p.L363S) alteration is located in exon 10 (coding exon 10) of the WDR70 gene. This alteration results from a T to C substitution at nucleotide position 1088, causing the leucine (L) at amino acid position 363 to be replaced by a serine (S). 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	0.25
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	-1.0	N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.74	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.43	T;D
Sift4G	Benign	0.42	T;D
Polyphen		0.50	P;P
Vest4		0.53
MutPred		0.45		Loss of stability (P = 0.014);Loss of stability (P = 0.014);
MVP		0.27
MPC		0.60
ClinPred		0.79	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.54

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: chr5-37605336;