rs1244297243

Variant names:

• chr5-132823281-C-T
• rs1244297243
• NM_001172700.2:c.2195G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-132823281-C-T
• chr5-132823281-C-A

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.2195G>A​(p.Arg732Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,447,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SHROOM1 NM_001172700.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01
• 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=0.17325366).

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.2195G>A	p.Arg732Gln	missense	Exon 9 of 10	NP_001166171.1	Q2M3G4-1
	SHROOM1	NM_133456.3		c.2195G>A	p.Arg732Gln	missense	Exon 6 of 7	NP_597713.2	Q2M3G4-2
	SHROOM1	NM_001410779.1		c.1988G>A	p.Arg663Gln	missense	Exon 6 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.2195G>A	p.Arg732Gln	missense	Exon 9 of 10	ENSP00000367950.3	Q2M3G4-1
	SHROOM1	ENST00000319854.7	TSL:1	c.2195G>A	p.Arg732Gln	missense	Exon 6 of 7	ENSP00000324245.3	Q2M3G4-2
	SHROOM1	ENST00000617339.4	TSL:5	c.2195G>A	p.Arg732Gln	missense	Exon 7 of 8	ENSP00000478436.1	Q2M3G4-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000446 AC: 1 AN: 224204 AF XY: 0.00000803

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000100

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1447428 Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 2 AN XY: 720176

African (AFR) AF: 0.00 AC: 0 AN: 33360

American (AMR) AF: 0.00 AC: 0 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25968

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110458

Other (OTH) AF: 0.00 AC: 0 AN: 60154

GnomAD4 genome Cov.: 32

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	0.098
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.054
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.0
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.12
Sift	Benign	0.057	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.071
MutPred		0.49		Loss of MoRF binding (P = 0.0286)
MVP		0.44
MPC		1.0
ClinPred		0.51	D
GERP RS		3.9
Varity_R		0.11
gMVP		0.078
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs1244297243; hg19: chr5-132158973; COSMIC: COSV60580549; COSMIC: COSV60580549;