4-76436345-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_020859.4(SHROOM3):c.168+125G>T 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 1,060,848 control chromosomes in the GnomAD database, including 13,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (1921 hom., cov: 32)
  • Exomes 𝑓: 0.15 (11098 hom.)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.322

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=-0.45).
• BP6: Variant 4-76436345-G-T is Benign according to our data. Variant chr4-76436345-G-T is described in ClinVar as [Benign]. Clinvar id is 1280311.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
SHROOM3	NM_020859.4	c.168+125G>T		intron_variant		ENST00000296043.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHROOM3	ENST00000296043.7	c.168+125G>T		intron_variant		1	NM_020859.4	P1
SHROOM3	ENST00000466541.1	n.75+125G>T		intron_variant, non_coding_transcript_variant		3
SHROOM3	ENST00000497440.5	n.109+125G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23966 AN: 151826 Hom.: 1917 Cov.: 32

Gnomad AFR AF: 0.153

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: 137684 AN: 908904 Hom.: 11098 AF XY: 0.155 AC XY: 72132 AN XY: 466872

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.0715

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.158 AC: 23973 AN: 151944 Hom.: 1921 Cov.: 32 AF XY: 0.158 AC XY: 11707 AN XY: 74256

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.170

Alfa AF: 0.152 Hom.: 207

Bravo AF: 0.148

Asia WGS AF: 0.206 AC: 718 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.45
Cadd	Benign	7.1
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs189707263; hg19: chr4-77357498;