4-76436339-C-A

Position:

• chr4-76436339-C-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_020859.4(SHROOM3):​c.168+119C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,116,882 control chromosomes in the GnomAD database, including 13,744 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (1915 hom., cov: 32)
  • Exomes 𝑓: 0.15 (11829 hom.)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.328

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 4-76436339-C-A is Benign according to our data. Variant chr4-76436339-C-A is described in ClinVar as [Benign]. Clinvar id is 1179242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM3	NM_020859.4	c.168+119C>A		intron_variant		ENST00000296043.7	NP_065910.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM3	ENST00000296043.7	c.168+119C>A		intron_variant		1	NM_020859.4	ENSP00000296043	P1
SHROOM3	ENST00000466541.1	n.75+119C>A		intron_variant, non_coding_transcript_variant		3
SHROOM3	ENST00000497440.5	n.109+119C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23956 AN: 151900 Hom.: 1911 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.151 AC: 145521 AN: 964864 Hom.: 11829 AF XY: 0.154 AC XY: 76278 AN XY: 494954

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.0723

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.183

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.158 AC: 23963 AN: 152018 Hom.: 1915 Cov.: 32 AF XY: 0.158 AC XY: 11704 AN XY: 74300

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.169

Alfa AF: 0.0603 Hom.: 71

Asia WGS AF: 0.206 AC: 718 AN: 3476

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	8.6
DANN	Benign	0.63

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: rs554755626; hg19: chr4-77357492;