5-132824109-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001172700.2(SHROOM1):c.1552C>T(p.Pro518Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SHROOM1 NM_001172700.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0600

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044015616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHROOM1	NM_001172700.2	c.1552C>T	p.Pro518Ser	missense_variant	7/10	ENST00000378679.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHROOM1	ENST00000378679.8	c.1552C>T	p.Pro518Ser	missense_variant	7/10	1	NM_001172700.2	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 12, 2024

The c.1552C>T (p.P518S) alteration is located in exon 7 (coding exon 4) of the SHROOM1 gene. This alteration results from a C to T substitution at nucleotide position 1552, causing the proline (P) at amino acid position 518 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	2.0
Dann	Benign	0.35
DEOGEN2	Benign	0.011	T;T;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.056	N
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.044	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L;L;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.65	N;.;N;N
REVEL	Benign	0.016
Sift	Benign	0.51	T;.;T;T
Sift4G	Benign	0.84	T;T;T;T
Polyphen		0.0040	B;B;B;.
Vest4		0.17
MutPred		0.20		Gain of phosphorylation at P518 (P = 0.0522);Gain of phosphorylation at P518 (P = 0.0522);Gain of phosphorylation at P518 (P = 0.0522);.;
MVP		0.20
MPC		0.015
ClinPred		0.025	T
GERP RS		-0.29
Varity_R		0.028
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-132159801;