4-76436375-G-T

Position:

• chr4-76436375-G-T

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+155G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,050 control chromosomes in the GnomAD database, including 2,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2359 hom., cov: 32)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.268

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=-0.73).
• BP6: Variant 4-76436375-G-T is Benign according to our data. Variant chr4-76436375-G-T is described in ClinVar as [Benign]. Clinvar id is 1180265.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	Protein	UniProt
SHROOM3	NM_020859.4	c.168+155G>T		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+155G>T		intron_variant		1	NM_020859.4	ENSP00000296043	P1
SHROOM3	ENST00000466541.1	n.75+155G>T		intron_variant, non_coding_transcript_variant		3
SHROOM3	ENST00000497440.5	n.109+155G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26194 AN: 151932 Hom.: 2354 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.172 AC: 26214 AN: 152050 Hom.: 2359 Cov.: 32 AF XY: 0.172 AC XY: 12786 AN XY: 74328

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.182

Alfa AF: 0.158 Hom.: 434

Asia WGS AF: 0.209 AC: 727 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	-0.73
CADD	Benign	1.2
DANN	Benign	0.65

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: rs11944802; hg19: chr4-77357528;