5-132823884-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001172700.2(SHROOM1):c.1777G>A(p.Ala593Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00675 in 1,534,540 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A593V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0049 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0069 ( 39 hom. )

Consequence

SHROOM1
NM_001172700.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.175

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046468377).

BP6

Variant 5-132823884-C-T is Benign according to our data. Variant chr5-132823884-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 771153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHROOM1	NM_001172700.2 linkuse as main transcript	c.1777G>A	p.Ala593Thr	missense_variant	7/10	ENST00000378679.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHROOM1	ENST00000378679.8 linkuse as main transcript	c.1777G>A	p.Ala593Thr	missense_variant	7/10	1	NM_001172700.2	P2	Q2M3G4-1
SHROOM1	ENST00000319854.7 linkuse as main transcript	c.1777G>A	p.Ala593Thr	missense_variant	4/7	1		A2	Q2M3G4-2
SHROOM1	ENST00000617339.4 linkuse as main transcript	c.1777G>A	p.Ala593Thr	missense_variant	5/8	5		P2	Q2M3G4-1
SHROOM1	ENST00000378676.1 linkuse as main transcript	c.1570G>A	p.Ala524Thr	missense_variant	3/6	5		A2

Frequencies

GnomAD3 genomes

AF:

0.00496

AC:

755

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00786

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00537

AC:

1012

AN:

188618

Hom.:

AF XY:

0.00560

AC XY:

557

AN XY:

99446

show subpopulations

Gnomad AFR exome

AF:

0.000983

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.000232

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000543

Gnomad FIN exome

AF:

0.00958

Gnomad NFE exome

AF:

0.00847

Gnomad OTH exome

AF:

0.00571

GnomAD4 exome

AF:

0.00695

AC:

9602

AN:

1382206

Hom.:

Cov.:

AF XY:

0.00679

AC XY:

4609

AN XY:

678642

show subpopulations

Gnomad4 AFR exome

AF:

0.00113

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00120

Gnomad4 FIN exome

AF:

0.0103

Gnomad4 NFE exome

AF:

0.00797

Gnomad4 OTH exome

AF:

0.00582

GnomAD4 genome

AF:

0.00495

AC:

754

AN:

152334

Hom.:

Cov.:

AF XY:

0.00478

AC XY:

356

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.00785

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00641

Hom.:

Bravo

AF:

0.00415

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00651

AC:

ExAC

AF:

0.00529

AC:

638

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	SHROOM1: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	May 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.015

T;T;.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.21

M_CAP

Benign

0.010

MetaRNN

Benign

0.0046

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.3

L;L;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

0.11

N;.;N;N

REVEL

Benign

0.040

Sift

Benign

0.28

T;.;T;T

Sift4G

Benign

0.065

T;T;T;T

Polyphen

0.23

B;B;B;.

Vest4

0.13

MVP

0.33

MPC

0.032

ClinPred

0.012

GERP RS

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.036

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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