5-132823360-T-G

Variant names:

• chr5-132823360-T-G
• rs764445525
• NM_001172700.2:c.2116A>C

Variant summary

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

The NM_001172700.2(SHROOM1):​c.2116A>C​(p.Met706Leu) 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 1,455,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• 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: 0.227

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=0.20700023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM1	NM_001172700.2	c.2116A>C	p.Met706Leu	missense_variant	Exon 9 of 10	ENST00000378679.8	NP_001166171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHROOM1	ENST00000378679.8	c.2116A>C	p.Met706Leu	missense_variant	Exon 9 of 10	1	NM_001172700.2	ENSP00000367950.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000857 AC: 2 AN: 233360 Hom.: 0 AF XY: 0.00000776 AC XY: 1 AN XY: 128894

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000586

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455578 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724364

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000829 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.033	T;T;.;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.60	.;T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;L;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.25	N;.;N;N
REVEL	Benign	0.044
Sift	Uncertain	0.010	D;.;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.0070	B;B;B;.
Vest4		0.30
MutPred		0.43		Loss of MoRF binding (P = 0.0797);Loss of MoRF binding (P = 0.0797);Loss of MoRF binding (P = 0.0797);.;
MVP		0.31
MPC		0.61
ClinPred		0.24	T
GERP RS		-0.91
Varity_R		0.25
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs764445525; hg19: chr5-132159052;