chr5-132823005-C-G

Variant names:

• chr5-132823005-C-G
• rs953659192
• NM_001172700.2:c.2350G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.355
• Publications: 0 publications found

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]

ACMG classification

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=0.24002716).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172700.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM1	NM_001172700.2	MANE Select	c.2350G>C	p.Glu784Gln	missense	Exon 10 of 10	NP_001166171.1	Q2M3G4-1
	SHROOM1	NM_133456.3		c.2335G>C	p.Glu779Gln	missense	Exon 7 of 7	NP_597713.2	Q2M3G4-2
	SHROOM1	NM_001410779.1		c.2143G>C	p.Glu715Gln	missense	Exon 7 of 7	NP_001397708.1	A6NN40

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM1	ENST00000378679.8	TSL:1 MANE Select	c.2350G>C	p.Glu784Gln	missense	Exon 10 of 10	ENSP00000367950.3	Q2M3G4-1
	SHROOM1	ENST00000319854.7	TSL:1	c.2335G>C	p.Glu779Gln	missense	Exon 7 of 7	ENSP00000324245.3	Q2M3G4-2
	SHROOM1	ENST00000617339.4	TSL:5	c.2350G>C	p.Glu784Gln	missense	Exon 8 of 8	ENSP00000478436.1	Q2M3G4-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 32

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: 1 AN: 1452810 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723118

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111638

Other (OTH) AF: 0.00 AC: 0 AN: 60262

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.35
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.11
Sift	Benign	0.036	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.44	B
Vest4		0.10
MutPred		0.73		Gain of catalytic residue at E784 (P = 0.0076)
MVP		0.48
MPC		1.1
ClinPred		0.50	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.11
gMVP		0.14
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs953659192; hg19: chr5-132158697;