5-132822900-C-T

Variant names:

• chr5-132822900-C-T
• rs750474444
• NM_001172700.2:c.2455G>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.2455G>A​(p.Ala819Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,178 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. A819S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SHROOM1 NM_001172700.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374
• 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=0.095196426).

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.2455G>A	p.Ala819Thr	missense	Exon 10 of 10	NP_001166171.1	Q2M3G4-1
	SHROOM1	NM_133456.3		c.2440G>A	p.Ala814Thr	missense	Exon 7 of 7	NP_597713.2	Q2M3G4-2
	SHROOM1	NM_001410779.1		c.2248G>A	p.Ala750Thr	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.2455G>A	p.Ala819Thr	missense	Exon 10 of 10	ENSP00000367950.3	Q2M3G4-1
	SHROOM1	ENST00000319854.7	TSL:1	c.2440G>A	p.Ala814Thr	missense	Exon 7 of 7	ENSP00000324245.3	Q2M3G4-2
	SHROOM1	ENST00000617339.4	TSL:5	c.2455G>A	p.Ala819Thr	missense	Exon 8 of 8	ENSP00000478436.1	Q2M3G4-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461178 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726894

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.37
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.13
Sift	Benign	0.29	T
Sift4G	Benign	0.49	T
Polyphen		0.73	P
Vest4		0.086
MutPred		0.70		Gain of phosphorylation at A819 (P = 0.0805)
MVP		0.40
MPC		0.64
ClinPred		0.12	T
GERP RS		2.1
Varity_R		0.045
gMVP		0.066
Mutation Taster		=92/8	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: rs750474444; hg19: chr5-132158592;