4-76731066-T-C

Position:

• chr4-76731066-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020859.4(SHROOM3):​c.587+131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,233,154 control chromosomes in the GnomAD database, including 95,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9045 hom., cov: 32)
  • Exomes 𝑓: 0.38 (86703 hom.)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.792

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]

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

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-76731066-T-C is Benign according to our data. Variant chr4-76731066-T-C is described in ClinVar as [Benign]. Clinvar id is 1236225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM3	NM_020859.4	c.587+131T>C		intron_variant		ENST00000296043.7	NP_065910.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM3	ENST00000296043.7	c.587+131T>C		intron_variant		1	NM_020859.4	ENSP00000296043	P1
SHROOM3-AS1	ENST00000666924.1	n.448+11742A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48601 AN: 151996 Hom.: 9040 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.384 AC: 415240 AN: 1081040 Hom.: 86703 AF XY: 0.381 AC XY: 210616 AN XY: 552906

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.551

Gnomad4 EAS exome AF: 0.0134

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.423

Gnomad4 OTH exome AF: 0.373

GnomAD4 genome AF: 0.320 AC: 48616 AN: 152114 Hom.: 9045 Cov.: 32 AF XY: 0.315 AC XY: 23394 AN XY: 74370

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.0283

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.350

Alfa AF: 0.410 Hom.: 27485

Bravo AF: 0.315

Asia WGS AF: 0.139 AC: 486 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.88
DANN	Benign	0.36

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: rs344135; hg19: chr4-77652219;