Genetic Variant SHROOM1:p.Ala678Ala (chr5-132823442-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001172700.2(SHROOM1):c.2034G>A(p.Ala678Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,612,108 control chromosomes in the GnomAD database, including 16,794 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1183 hom., cov: 33)

Exomes 𝑓: 0.14 ( 15611 hom. )

Consequence

SHROOM1
NM_001172700.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.17

Publications

14 publications found

Variant links:

Genes affected

SHROOM1 (HGNC:24084): (shroom family member 1) SHROOM family members play diverse roles in the development of the nervous system and other tissues (Hagens et al., 2006 [PubMed 16615870]).[supplied by OMIM, Mar 2008]

SHROOM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP7

Synonymous conserved (PhyloP=-2.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM1	NM_001172700.2 link	c.2034G>A	p.Ala678Ala	synonymous_variant	Exon 9 of 10	ENST00000378679.8	NP_001166171.1	Q2M3G4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHROOM1	ENST00000378679.8 link	c.2034G>A	p.Ala678Ala	synonymous_variant	Exon 9 of 10	1	NM_001172700.2	ENSP00000367950.3		Q2M3G4-1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17552

AN:

152156

Hom.:

1184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0583

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.0907

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.145

Gnomad OTH

AF:

0.135

GnomAD2 exomes

AF:

0.136

AC:

33001

AN:

243242

AF XY:

0.142

show subpopulations

Gnomad AFR exome

AF:

0.0569

Gnomad AMR exome

AF:

0.0742

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.144

AC:

209769

AN:

1459834

Hom.:

15611

Cov.:

AF XY:

0.147

AC XY:

106424

AN XY:

726234

show subpopulations

African (AFR)

AF:

0.0571

AC:

1913

AN:

33474

American (AMR)

AF:

0.0755

AC:

3373

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

3550

AN:

26108

East Asian (EAS)

AF:

0.123

AC:

4898

AN:

39696

South Asian (SAS)

AF:

0.194

AC:

16723

AN:

86224

European-Finnish (FIN)

AF:

0.138

AC:

7158

AN:

51708

Middle Eastern (MID)

AF:

0.209

AC:

1201

AN:

5744

European-Non Finnish (NFE)

AF:

0.146

AC:

162498

AN:

1111834

Other (OTH)

AF:

0.140

AC:

8455

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

12080

24159

36239

48318

60398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5776

11552

17328

23104

28880

<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:

0.115

AC:

17562

AN:

152274

Hom.:

1183

Cov.:

AF XY:

0.117

AC XY:

8677

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0583

AC:

2425

AN:

41570

American (AMR)

AF:

0.0905

AC:

1386

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

488

AN:

3468

East Asian (EAS)

AF:

0.116

AC:

602

AN:

5168

South Asian (SAS)

AF:

0.197

AC:

953

AN:

4830

European-Finnish (FIN)

AF:

0.128

AC:

1357

AN:

10592

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.145

AC:

9887

AN:

68014

Other (OTH)

AF:

0.134

AC:

283

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

827

1653

2480

3306

4133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<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:

0.128

Hom.:

1968

Bravo

AF:

0.108

Asia WGS

AF:

0.134

AC:

466

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.3

(source)

DANN

Benign

0.62

PhyloP100

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over