4-76436439-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020859.4(SHROOM3):c.168+219T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,068 control chromosomes in the GnomAD database, including 8,211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (8211 hom., cov: 32)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.146

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-76436439-T-C is Benign according to our data. Variant chr4-76436439-T-C is described in ClinVar as [Benign]. Clinvar id is 1286515.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHROOM3	NM_020859.4	c.168+219T>C		intron_variant		ENST00000296043.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHROOM3	ENST00000296043.7	c.168+219T>C		intron_variant		1	NM_020859.4	P1
SHROOM3	ENST00000466541.1	n.75+219T>C		intron_variant, non_coding_transcript_variant		3
SHROOM3	ENST00000497440.5	n.109+219T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46166 AN: 151950 Hom.: 8205 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.304 AC: 46199 AN: 152068 Hom.: 8211 Cov.: 32 AF XY: 0.299 AC XY: 22235 AN XY: 74334

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.306

Alfa AF: 0.371 Hom.: 2352

Bravo AF: 0.298

Asia WGS AF: 0.116 AC: 405 AN: 3474

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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.9
Dann	Benign	0.37

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: rs10019833; hg19: chr4-77357592;