5-132823442-C-T

Position:

• chr5-132823442-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001172700.2(SHROOM1):​c.2034G>A​(p.Ala678=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,612,108 control chromosomes in the GnomAD database, including 16,794 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1183 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15611 hom.)
• Consequence: SHROOM1 NM_001172700.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-2.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM1	NM_001172700.2	c.2034G>A	p.Ala678=	synonymous_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.2034G>A	p.Ala678=	synonymous_variant	9/10	1	NM_001172700.2	ENSP00000367950	P2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17552 AN: 152156 Hom.: 1184 Cov.: 33

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0907

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.135

GnomAD3 exomes AF: 0.136 AC: 33001 AN: 243242 Hom.: 2530 AF XY: 0.142 AC XY: 18921 AN XY: 133066

Gnomad AFR exome AF: 0.0569

Gnomad AMR exome AF: 0.0742

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.118

Gnomad SAS exome AF: 0.197

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.152

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.144 AC: 209769 AN: 1459834 Hom.: 15611 Cov.: 33 AF XY: 0.147 AC XY: 106424 AN XY: 726234

Gnomad4 AFR exome AF: 0.0571

Gnomad4 AMR exome AF: 0.0755

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.115 AC: 17562 AN: 152274 Hom.: 1183 Cov.: 33 AF XY: 0.117 AC XY: 8677 AN XY: 74446

Gnomad4 AFR AF: 0.0583

Gnomad4 AMR AF: 0.0905

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.134

Alfa AF: 0.131 Hom.: 1661

Bravo AF: 0.108

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.3
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4705870; hg19: chr5-132159134; COSMIC: COSV60580424; COSMIC: COSV60580424;