5-132823410-G-A

Position:

• chr5-132823410-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001172700.2(SHROOM1):​c.2066C>T​(p.Ala689Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SHROOM1 NM_001172700.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00100

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17980441).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM1	NM_001172700.2	c.2066C>T	p.Ala689Val	missense_variant	9/10	ENST00000378679.8	NP_001166171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM1	ENST00000378679.8	c.2066C>T	p.Ala689Val	missense_variant	9/10	1	NM_001172700.2	ENSP00000367950	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458634 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 725724

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Aug 23, 2021

The c.2066C>T (p.A689V) alteration is located in exon 9 (coding exon 6) of the SHROOM1 gene. This alteration results from a C to T substitution at nucleotide position 2066, causing the alanine (A) at amino acid position 689 to be replaced by a valine (V). 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	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T;T;.;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.71	.;T;T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.95	N;.;N;N
REVEL	Benign	0.11
Sift	Benign	0.20	T;.;T;T
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.98	D;D;P;.
Vest4		0.13
MutPred		0.58		Loss of disorder (P = 0.0496);Loss of disorder (P = 0.0496);Loss of disorder (P = 0.0496);.;
MVP		0.35
MPC		0.82
ClinPred		0.33	T
GERP RS		1.1
Varity_R		0.027
gMVP		0.096

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-132159102;