18-56695094-A-T

Variant names:

• chr18-56695094-A-T
• rs762232596
• NM_015285.3:c.1253A>T

Variant summary

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

The NM_015285.3(WDR7):​c.1253A>T​(p.His418Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 32)
• Consequence: WDR7 NM_015285.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.06

Genes affected

WDR7 (HGNC:13490): (WD repeat domain 7) 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) that 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. The encoded protein forms the beta subunit of rabconnectin-3 and binds directly with Rab3A GDP/GTP exchange protein and indirectly with Rab3A GDP/GTP activating protein; these proteins are regulators of Rab3 small G protein family members involved in control of the calcium-dependant exocytosis of neurotransmitters. Alternatively spliced transcript variants encoding different isoforms have been described. [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=0.17966208).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR7	NM_015285.3	c.1253A>T	p.His418Leu	missense_variant	Exon 11 of 28	ENST00000254442.8	NP_056100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR7	ENST00000254442.8	c.1253A>T	p.His418Leu	missense_variant	Exon 11 of 28	1	NM_015285.3	ENSP00000254442.3
WDR7	ENST00000357574.7	c.1253A>T	p.His418Leu	missense_variant	Exon 11 of 27	5		ENSP00000350187.2
WDR7	ENST00000589935.1	c.-1+43518A>T		intron_variant	Intron 1 of 1	4		ENSP00000467485.1
WDR7	ENST00000585754.1	n.259A>T		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74332

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: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.092	.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.051
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.46	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.20
Sift	Uncertain	0.016	D;D
Sift4G	Uncertain	0.037	D;D
Polyphen		0.040	B;P
Vest4		0.47
MutPred		0.62		Loss of methylation at R420 (P = 0.0636);Loss of methylation at R420 (P = 0.0636);
MVP		0.082
MPC		0.55
ClinPred		0.78	D
GERP RS		5.4
Varity_R		0.26
gMVP		0.65

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: rs762232596; hg19: chr18-54362325;