Genetic Variant NM_015238.3:c.-6G>A (chr5-168292147-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_015238.3(WWC1):c.-6G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000399 in 1,538,332 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 4 hom. )

Consequence

WWC1
NM_015238.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.112

Publications

0 publications found

Variant links:

Genes affected

WWC1 (HGNC:29435): (WW and C2 domain containing 1) The protein encoded by this gene is a cytoplasmic phosphoprotein that interacts with PRKC-zeta and dynein light chain-1. Alleles of this gene have been found that enhance memory in some individuals. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

WWC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 5-168292147-G-A is Benign according to our data. Variant chr5-168292147-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2656034.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015238.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WWC1	NM_015238.3	MANE Select	c.-6G>A	5_prime_UTR	Exon 1 of 23	NP_056053.1	Q8IX03-1
WWC1	NM_001161661.2		c.-6G>A	5_prime_UTR	Exon 1 of 23	NP_001155133.1	Q8IX03-2
WWC1	NM_001161662.2		c.-6G>A	5_prime_UTR	Exon 1 of 23	NP_001155134.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WWC1	ENST00000265293.9	TSL:1 MANE Select	c.-6G>A	5_prime_UTR	Exon 1 of 23	ENSP00000265293.4	Q8IX03-1
WWC1	ENST00000917779.1		c.-6G>A	5_prime_UTR	Exon 1 of 23	ENSP00000587838.1
WWC1	ENST00000917783.1		c.-6G>A	5_prime_UTR	Exon 1 of 23	ENSP00000587842.1

Frequencies

GnomAD3 genomes

AF:

0.00199

AC:

303

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.0000589

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000363

AC:

AN:

137886

AF XY:

0.000190

show subpopulations

Gnomad AFR exome

AF:

0.00660

Gnomad AMR exome

AF:

0.000219

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000391

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000224

AC:

311

AN:

1386186

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

142

AN XY:

683520

show subpopulations

African (AFR)

AF:

0.00739

AC:

222

AN:

30044

American (AMR)

AF:

0.000346

AC:

AN:

34728

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24782

East Asian (EAS)

AF:

0.00

AC:

AN:

34370

South Asian (SAS)

AF:

0.0000258

AC:

AN:

77370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47920

Middle Eastern (MID)

AF:

0.000359

AC:

AN:

5566

European-Non Finnish (NFE)

AF:

0.0000279

AC:

AN:

1073900

Other (OTH)

AF:

0.000748

AC:

AN:

57506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00199

AC:

303

AN:

152146

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

147

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00698

AC:

290

AN:

41550

American (AMR)

AF:

0.000458

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67952

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000693

Hom.:

Bravo

AF:

0.00233

Asia WGS

AF:

0.000289

AC:

AN:

3470

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.11

PromoterAI

0.025

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over