rs1244297243

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001172700.2(SHROOM1):​c.2195G>T​(p.Arg732Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R732Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SHROOM1
NM_001172700.2 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35033756).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SHROOM1NM_001172700.2 linkc.2195G>T p.Arg732Leu missense_variant Exon 9 of 10 ENST00000378679.8 NP_001166171.1 Q2M3G4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SHROOM1ENST00000378679.8 linkc.2195G>T p.Arg732Leu missense_variant Exon 9 of 10 1 NM_001172700.2 ENSP00000367950.3 Q2M3G4-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152246
Hom.:
0
Cov.:
32
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1447428
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
720176
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152246
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74388
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:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
T;T;.;T
Eigen
Benign
0.090
Eigen_PC
Benign
-0.015
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.76
.;T;T;T
M_CAP
Benign
0.072
D
MetaRNN
Benign
0.35
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.6
M;M;M;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.6
D;.;D;D
REVEL
Benign
0.089
Sift
Benign
0.034
D;.;D;T
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
D;D;P;.
Vest4
0.36
MutPred
0.60
Loss of MoRF binding (P = 0.0073);Loss of MoRF binding (P = 0.0073);Loss of MoRF binding (P = 0.0073);.;
MVP
0.52
MPC
1.7
ClinPred
0.95
D
GERP RS
3.9
Varity_R
0.26
gMVP
0.18

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.

Other links and lift over

dbSNP: rs1244297243; hg19: chr5-132158973; API