Genetic Variant SHROOM3:p.Gly279Asp (chr4-76739009-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020859.4(SHROOM3):c.836G>A(p.Gly279Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G279A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

SHROOM3
NM_020859.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.849

Publications

36 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11270228).

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	HGVSp	Effect	Exon Rank	Protein
SHROOM3	NM_020859.4	MANE Select	c.836G>A	p.Gly279Asp	missense	Exon 5 of 11	NP_065910.3
SHROOM3-AS1	NR_187404.1		n.1044+3799C>T		intron	N/A
SHROOM3-AS1	NR_187405.1		n.500+3799C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SHROOM3	ENST00000296043.7	TSL:1 MANE Select	c.836G>A	p.Gly279Asp	missense	Exon 5 of 11	ENSP00000296043.6
SHROOM3	ENST00000646790.1		c.593G>A	p.Gly198Asp	missense	Exon 4 of 10	ENSP00000494970.1
SHROOM3	ENST00000486758.5	TSL:2	n.645G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152060

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:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.2

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.14

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.64

M_CAP

Benign

0.015

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.0

PhyloP100

0.85

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.1

REVEL

Benign

0.13

Sift

Uncertain

0.0060

Sift4G

Benign

0.22

Polyphen

0.65

Vest4

0.15

MutPred

0.13

Loss of glycosylation at S278 (P = 0.0232)

MVP

0.23

MPC

0.72

ClinPred

0.16

GERP RS

-0.95

Varity_R

0.088

gMVP

0.084

Mutation Taster

=98/2

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over