chr4-76476862-A-G

Variant names:

• chr4-76476862-A-G
• rs10032549
• NM_020859.4:c.168+40642A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020859.4(SHROOM3):​c.168+40642A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,028 control chromosomes in the GnomAD database, including 14,985 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14985 hom., cov: 32)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• neural tube defect

  Inheritance: AD Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM3	NM_020859.4	c.168+40642A>G		intron_variant	Intron 1 of 10	ENST00000296043.7	NP_065910.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHROOM3	ENST00000296043.7	c.168+40642A>G		intron_variant	Intron 1 of 10	1	NM_020859.4	ENSP00000296043.6
SHROOM3	ENST00000466541.1	n.75+40642A>G		intron_variant	Intron 1 of 2	3
SHROOM3	ENST00000497440.5	n.109+40642A>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64916 AN: 151910 Hom.: 14973 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.427 AC: 64952 AN: 152028 Hom.: 14985 Cov.: 32 AF XY: 0.422 AC XY: 31361 AN XY: 74306

African (AFR) AF: 0.265 AC: 11013 AN: 41488

American (AMR) AF: 0.471 AC: 7199 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1675 AN: 3464

East Asian (EAS) AF: 0.297 AC: 1531 AN: 5158

South Asian (SAS) AF: 0.339 AC: 1631 AN: 4818

European-Finnish (FIN) AF: 0.476 AC: 5015 AN: 10546

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35629 AN: 67964

Other (OTH) AF: 0.432 AC: 908 AN: 2100

Alfa AF: 0.493 Hom.: 59241

Bravo AF: 0.424

Asia WGS AF: 0.289 AC: 1009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.53
PhyloP100		0.074
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10032549; hg19: chr4-77398015;