rs9992101

Positions:

• chr4-76439278-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+3058G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,038 control chromosomes in the GnomAD database, including 7,731 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 0.28 (7731 hom., cov: 31)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.699

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHROOM3	NM_020859.4	c.168+3058G>A		intron_variant		ENST00000296043.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHROOM3	ENST00000296043.7	c.168+3058G>A		intron_variant		1	NM_020859.4	P1
SHROOM3	ENST00000466541.1	n.75+3058G>A		intron_variant, non_coding_transcript_variant		3
SHROOM3	ENST00000497440.5	n.109+3058G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42773 AN: 151918 Hom.: 7729 Cov.: 31

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.281 AC: 42778 AN: 152038 Hom.: 7731 Cov.: 31 AF XY: 0.277 AC XY: 20588 AN XY: 74290

Gnomad4 AFR AF: 0.0755

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.289

Alfa AF: 0.378 Hom.: 13692

Bravo AF: 0.272

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.60
DANN	Benign	0.16

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: rs9992101; hg19: chr4-77360431;