Genetic Variant SHROOM3:c.587+131T>C (chr4-76731066-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020859.4(SHROOM3):c.587+131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,233,154 control chromosomes in the GnomAD database, including 95,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 9045 hom., cov: 32)

Exomes 𝑓: 0.38 ( 86703 hom. )

Consequence

SHROOM3
NM_020859.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.792

Publications

2 publications found

Variant links:

Genes affected

SHROOM3 (HGNC:30422): (shroom family member 3) This gene encodes a PDZ-domain-containing protein that belongs to a family of Shroom-related proteins. This protein may be involved in regulating cell shape in certain tissues. A similar protein in mice is required for proper neurulation. [provided by RefSeq, Jan 2011]

SHROOM3 links:

SHROOM3-AS1 (HGNC:41265): (SHROOM3 antisense RNA 1)

SHROOM3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 4-76731066-T-C is Benign according to our data. Variant chr4-76731066-T-C is described in ClinVar as Benign. ClinVar VariationId is 1236225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020859.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SHROOM3	NM_020859.4	MANE Select	c.587+131T>C	intron	N/A	NP_065910.3	Q8TF72-1
SHROOM3-AS1	NR_187404.1		n.1044+11742A>G	intron	N/A
SHROOM3-AS1	NR_187405.1		n.500+11742A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SHROOM3	ENST00000296043.7	TSL:1 MANE Select	c.587+131T>C	intron	N/A	ENSP00000296043.6	Q8TF72-1
SHROOM3	ENST00000912766.1		c.590+131T>C	intron	N/A	ENSP00000582825.1
SHROOM3	ENST00000646790.1		c.344+131T>C	intron	N/A	ENSP00000494970.1	A0A2R8Y5P9

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48601

AN:

151996

Hom.:

9040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.0283

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.353

GnomAD4 exome

AF:

0.384

AC:

415240

AN:

1081040

Hom.:

86703

AF XY:

0.381

AC XY:

210616

AN XY:

552906

show subpopulations

African (AFR)

AF:

0.148

AC:

3834

AN:

25894

American (AMR)

AF:

0.310

AC:

12425

AN:

40032

Ashkenazi Jewish (ASJ)

AF:

0.551

AC:

12553

AN:

22794

East Asian (EAS)

AF:

0.0134

AC:

480

AN:

35934

South Asian (SAS)

AF:

0.247

AC:

18956

AN:

76670

European-Finnish (FIN)

AF:

0.346

AC:

12604

AN:

36448

Middle Eastern (MID)

AF:

0.403

AC:

1965

AN:

4872

European-Non Finnish (NFE)

AF:

0.423

AC:

334794

AN:

791166

Other (OTH)

AF:

0.373

AC:

17629

AN:

47230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

12360

24720

37080

49440

61800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8748

17496

26244

34992

43740

<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:

0.320

AC:

48616

AN:

152114

Hom.:

9045

Cov.:

AF XY:

0.315

AC XY:

23394

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.158

AC:

6567

AN:

41502

American (AMR)

AF:

0.342

AC:

5228

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

1887

AN:

3470

East Asian (EAS)

AF:

0.0283

AC:

147

AN:

5186

South Asian (SAS)

AF:

0.241

AC:

1162

AN:

4828

European-Finnish (FIN)

AF:

0.354

AC:

3742

AN:

10564

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28587

AN:

67972

Other (OTH)

AF:

0.350

AC:

738

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1587

3174

4760

6347

7934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<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:

0.393

Hom.:

52991

Bravo

AF:

0.315

Asia WGS

AF:

0.139

AC:

486

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.88

(source)

DANN

Benign

0.36

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism (auto)

(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

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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