dbSNP rs7676973: SHROOM3:c.5350-65G>A (chr4-76770561-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020859.4(SHROOM3):c.5350-65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 1,595,528 control chromosomes in the GnomAD database, including 3,380 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 0.059 ( 292 hom., cov: 31)

Exomes 𝑓: 0.062 ( 3088 hom. )

Consequence

SHROOM3
NM_020859.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.569

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SHROOM3	NM_020859.4 link	c.5350-65G>A	intron_variant	Intron 9 of 10	ENST00000296043.7	NP_065910.3	Q8TF72-1B3KY47
SHROOM3-AS1	NR_187404.1 link	n.408-11969C>T	intron_variant	Intron 1 of 3
SHROOM3-AS1	NR_187405.1 link	n.408-27661C>T	intron_variant	Intron 1 of 2
SHROOM3-AS1	NR_187406.1 link	n.97-11969C>T	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHROOM3	ENST00000296043.7 link	c.5350-65G>A		intron_variant	Intron 9 of 10	1	NM_020859.4	ENSP00000296043.6		Q8TF72-1

Frequencies

GnomAD3 genomes

AF:

0.0590

AC:

8968

AN:

151932

Hom.:

293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0556

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.0415

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.00483

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.0733

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0707

Gnomad OTH

AF:

0.0561

GnomAD4 exome

AF:

0.0616

AC:

88941

AN:

1443478

Hom.:

3088

AF XY:

0.0605

AC XY:

43418

AN XY:

718068

show subpopulations

African (AFR)

AF:

0.0565

AC:

1878

AN:

33252

American (AMR)

AF:

0.0345

AC:

1516

AN:

43926

Ashkenazi Jewish (ASJ)

AF:

0.0348

AC:

905

AN:

25998

East Asian (EAS)

AF:

0.00804

AC:

318

AN:

39566

South Asian (SAS)

AF:

0.0163

AC:

1387

AN:

85162

European-Finnish (FIN)

AF:

0.0674

AC:

3187

AN:

47262

Middle Eastern (MID)

AF:

0.0316

AC:

139

AN:

4404

European-Non Finnish (NFE)

AF:

0.0691

AC:

76293

AN:

1104086

Other (OTH)

AF:

0.0555

AC:

3318

AN:

59822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

3850

7700

11550

15400

19250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2728

5456

8184

10912

13640

<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:

0.0590

AC:

8974

AN:

152050

Hom.:

292

Cov.:

AF XY:

0.0577

AC XY:

4290

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.0557

AC:

2310

AN:

41488

American (AMR)

AF:

0.0415

AC:

633

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0337

AC:

117

AN:

3472

East Asian (EAS)

AF:

0.00484

AC:

AN:

5162

South Asian (SAS)

AF:

0.0129

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0733

AC:

776

AN:

10582

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0707

AC:

4805

AN:

67954

Other (OTH)

AF:

0.0556

AC:

117

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

428

856

1283

1711

2139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0702

Hom.:

Bravo

AF:

0.0565

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.13

(source)

DANN

Benign

0.41

PhyloP100

-0.57

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over