5-132823005-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001172700.2(SHROOM1):​c.2350G>A​(p.Glu784Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,810 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E784Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SHROOM1 NM_001172700.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>A	p.Glu784Lys	missense	Exon 10 of 10	NP_001166171.1	Q2M3G4-1
	SHROOM1	NM_133456.3		c.2335G>A	p.Glu779Lys	missense	Exon 7 of 7	NP_597713.2	Q2M3G4-2
	SHROOM1	NM_001410779.1		c.2143G>A	p.Glu715Lys	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>A	p.Glu784Lys	missense	Exon 10 of 10	ENSP00000367950.3	Q2M3G4-1
	SHROOM1	ENST00000319854.7	TSL:1	c.2335G>A	p.Glu779Lys	missense	Exon 7 of 7	ENSP00000324245.3	Q2M3G4-2
	SHROOM1	ENST00000617339.4	TSL:5	c.2350G>A	p.Glu784Lys	missense	Exon 8 of 8	ENSP00000478436.1	Q2M3G4-1

Frequencies

GnomAD3 genomes Cov.: 32

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 Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.35
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.14
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.81	P
Vest4		0.14
MutPred		0.80		Gain of MoRF binding (P = 0.0029)
MVP		0.55
MPC		0.96
ClinPred		0.81	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.37
gMVP		0.22
Mutation Taster		=78/22	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: rs953659192; hg19: chr5-132158697;