Genetic Variant NM_001172700.2:c.2350G>C (chr5-132823005-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001172700.2(SHROOM1):c.2350G>C(p.Glu784Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,605,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SHROOM1
NM_001172700.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.355

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24002716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM1	NM_001172700.2 link	c.2350G>C	p.Glu784Gln	missense_variant	Exon 10 of 10	ENST00000378679.8	NP_001166171.1	Q2M3G4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SHROOM1	ENST00000378679.8 link	c.2350G>C	p.Glu784Gln	missense_variant	Exon 10 of 10	1	NM_001172700.2	ENSP00000367950.3	Q2M3G4-1
SHROOM1	ENST00000319854.7 link	c.2335G>C	p.Glu779Gln	missense_variant	Exon 7 of 7	1		ENSP00000324245.3	Q2M3G4-2
SHROOM1	ENST00000617339.4 link	c.2350G>C	p.Glu784Gln	missense_variant	Exon 8 of 8	5		ENSP00000478436.1	Q2M3G4-1
SHROOM1	ENST00000378676.1 link	c.2143G>C	p.Glu715Gln	missense_variant	Exon 6 of 6	5		ENSP00000367947.1	A6NN40

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1452810

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2350G>C (p.E784Q) alteration is located in exon 10 (coding exon 7) of the SHROOM1 gene. This alteration results from a G to C substitution at nucleotide position 2350, causing the glutamic acid (E) at amino acid position 784 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;T;.;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.60

.;T;T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.24

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.1

M;M;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.4

N;.;N;D

REVEL

Benign

0.11

Sift

Benign

0.036

D;.;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.44

B;B;B;.

Vest4

0.10

MutPred

0.73

Gain of catalytic residue at E784 (P = 0.0076);Gain of catalytic residue at E784 (P = 0.0076);.;.;

MVP

0.48

MPC

1.1

ClinPred

0.50

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.11

gMVP

0.14

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

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