NM_015285.3:c.396C>T

Variant names:

• chr18-56682729-C-T
• rs140122275
• NM_015285.3:c.396C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_015285.3(WDR7):​c.396C>T​(p.His132His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,613,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: WDR7 NM_015285.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.951
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 18-56682729-C-T is Benign according to our data. Variant chr18-56682729-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2648742.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.951 with no splicing effect.
• BS2: High AC in GnomAd4 at 38 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015285.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR7	NM_015285.3	MANE Select	c.396C>T	p.His132His	synonymous	Exon 5 of 28	NP_056100.2	Q9Y4E6-1
	WDR7	NM_001382487.1		c.396C>T	p.His132His	synonymous	Exon 5 of 28	NP_001369416.1	Q9Y4E6-1
	WDR7	NM_001382485.1		c.396C>T	p.His132His	synonymous	Exon 5 of 27	NP_001369414.1	Q9Y4E6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR7	ENST00000254442.8	TSL:1 MANE Select	c.396C>T	p.His132His	synonymous	Exon 5 of 28	ENSP00000254442.3	Q9Y4E6-1
	WDR7	ENST00000357574.7	TSL:5	c.396C>T	p.His132His	synonymous	Exon 5 of 27	ENSP00000350187.2	Q9Y4E6-2
	WDR7	ENST00000593058.1	TSL:3	c.396C>T	p.His132His	synonymous	Exon 5 of 5	ENSP00000466438.1	K7EMB8

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000386 AC: 97 AN: 251178 AF XY: 0.000390

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00705

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000881

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000220 AC: 322 AN: 1461542 Hom.: 0 Cov.: 31 AF XY: 0.000212 AC XY: 154 AN XY: 727064

African (AFR) AF: 0.000149 AC: 5 AN: 33460

American (AMR) AF: 0.000313 AC: 14 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00758 AC: 198 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.0000621 AC: 69 AN: 1111786

Other (OTH) AF: 0.000547 AC: 33 AN: 60382

GnomAD4 genome AF: 0.000250 AC: 38 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74458

African (AFR) AF: 0.0000481 AC: 2 AN: 41570

American (AMR) AF: 0.000196 AC: 3 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000788 Hom.: 0

Bravo AF: 0.000321

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	5.8
DANN	Benign	0.68
PhyloP100		-0.95
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs140122275; hg19: chr18-54349960;