rs7676973

Positions:

• chr4-76770561-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.5350-65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 1,595,528 control chromosomes in the GnomAD database, including 3,380 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 0.059 (292 hom., cov: 31)
  • Exomes 𝑓: 0.062 (3088 hom.)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569

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]

ENSG00000224218 (HGNC:):

SHROOM3-AS1 (HGNC:41265): (SHROOM3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM3	NM_020859.4	c.5350-65G>A		intron_variant		ENST00000296043.7	NP_065910.3
SHROOM3-AS1	NR_187404.1	n.408-11969C>T		intron_variant
SHROOM3-AS1	NR_187405.1	n.408-27661C>T		intron_variant
SHROOM3-AS1	NR_187406.1	n.97-11969C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM3	ENST00000296043.7	c.5350-65G>A		intron_variant		1	NM_020859.4	ENSP00000296043.6

Frequencies

GnomAD3 genomes AF: 0.0590 AC: 8968 AN: 151932 Hom.: 293 Cov.: 31

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.00483

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0707

Gnomad OTH AF: 0.0561

GnomAD4 exome AF: 0.0616 AC: 88941 AN: 1443478 Hom.: 3088 AF XY: 0.0605 AC XY: 43418 AN XY: 718068

Gnomad4 AFR exome AF: 0.0565

Gnomad4 AMR exome AF: 0.0345

Gnomad4 ASJ exome AF: 0.0348

Gnomad4 EAS exome AF: 0.00804

Gnomad4 SAS exome AF: 0.0163

Gnomad4 FIN exome AF: 0.0674

Gnomad4 NFE exome AF: 0.0691

Gnomad4 OTH exome AF: 0.0555

GnomAD4 genome AF: 0.0590 AC: 8974 AN: 152050 Hom.: 292 Cov.: 31 AF XY: 0.0577 AC XY: 4290 AN XY: 74332

Gnomad4 AFR AF: 0.0557

Gnomad4 AMR AF: 0.0415

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.00484

Gnomad4 SAS AF: 0.0129

Gnomad4 FIN AF: 0.0733

Gnomad4 NFE AF: 0.0707

Gnomad4 OTH AF: 0.0556

Alfa AF: 0.0707 Hom.: 61

Bravo AF: 0.0565

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.41

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: rs7676973; hg19: chr4-77691714;