rs13146355

chr4-76490987-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020859.4(SHROOM3):c.168+54767G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,054 control chromosomes in the GnomAD database, including 9,750 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 0.33 (9750 hom., cov: 32)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

Genes affected

SHROOM3 (HGNC:30422): (shroom family member 3) This gene encodes a PDZ-domain-containing protein that belongs to a family of Shroom-related proteins. This protein may be involved in regulating cell shape in certain tissues. A similar protein in mice is required for proper neurulation. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHROOM3	NM_020859.4	c.168+54767G>A		intron_variant		ENST00000296043.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHROOM3	ENST00000296043.7	c.168+54767G>A		intron_variant		1	NM_020859.4	P1
SHROOM3	ENST00000466541.1	n.75+54767G>A		intron_variant, non_coding_transcript_variant		3
SHROOM3	ENST00000497440.5	n.109+54767G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50249 AN: 151936 Hom.: 9745 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.335

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50267 AN: 152054 Hom.: 9750 Cov.: 32 AF XY: 0.326 AC XY: 24236 AN XY: 74300

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.332

Alfa AF: 0.420 Hom.: 16418

Bravo AF: 0.321

Asia WGS AF: 0.182 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	9.4
Dann	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs13146355; hg19: chr4-77412140;