dbSNP rs344135: SHROOM3:c.587+131T>C (chr4-76731066-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SHROOM3	NM_020859.4 link	c.587+131T>C	intron_variant	Intron 4 of 10	ENST00000296043.7	NP_065910.3	Q8TF72-1B3KY47
SHROOM3-AS1	NR_187404.1 link	n.1044+11742A>G	intron_variant	Intron 3 of 3
SHROOM3-AS1	NR_187405.1 link	n.500+11742A>G	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHROOM3	ENST00000296043.7 link	c.587+131T>C		intron_variant	Intron 4 of 10	1	NM_020859.4	ENSP00000296043.6		Q8TF72-1

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

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.310

Gnomad4 ASJ exome

AF:

0.551

Gnomad4 EAS exome

AF:

0.0134

Gnomad4 SAS exome

AF:

0.247

Gnomad4 FIN exome

AF:

0.346

Gnomad4 NFE exome

AF:

0.423

Gnomad4 OTH exome

AF:

0.373

GnomAD4 genome

AF:

0.320

AC:

48616

AN:

152114

Hom.:

9045

Cov.:

AF XY:

0.315

AC XY:

23394

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.342

Gnomad4 ASJ

AF:

0.544

Gnomad4 EAS

AF:

0.0283

Gnomad4 SAS

AF:

0.241

Gnomad4 FIN

AF:

0.354

Gnomad4 NFE

AF:

0.421

Gnomad4 OTH

AF:

0.350

Alfa

AF:

0.410

Hom.:

27485

Bravo

AF:

0.315

Asia WGS

AF:

0.139

AC:

486

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.88

DANN

Benign

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over