4-76499631-C-T

Variant names:

• chr4-76499631-C-T
• rs1986734
• NM_020859.4:c.169-55978C>T

Variant summary

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

The NM_020859.4(SHROOM3):​c.169-55978C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,022 control chromosomes in the GnomAD database, including 15,466 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 (15466 hom., cov: 32)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 22 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM3	NM_020859.4	c.169-55978C>T		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.169-55978C>T		intron_variant	Intron 1 of 10	1	NM_020859.4	ENSP00000296043.6
SHROOM3	ENST00000466541.1	n.76-55978C>T		intron_variant	Intron 1 of 2	3
SHROOM3	ENST00000497440.5	n.110-55978C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65617 AN: 151904 Hom.: 15462 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.432 AC: 65657 AN: 152022 Hom.: 15466 Cov.: 32 AF XY: 0.432 AC XY: 32140 AN XY: 74326

African (AFR) AF: 0.245 AC: 10160 AN: 41456

American (AMR) AF: 0.434 AC: 6634 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1682 AN: 3468

East Asian (EAS) AF: 0.562 AC: 2902 AN: 5162

South Asian (SAS) AF: 0.411 AC: 1977 AN: 4816

European-Finnish (FIN) AF: 0.545 AC: 5753 AN: 10564

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35321 AN: 67972

Other (OTH) AF: 0.431 AC: 909 AN: 2110

Alfa AF: 0.493 Hom.: 62665

Bravo AF: 0.419

Asia WGS AF: 0.446 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.49
PhyloP100		-0.36
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: rs1986734; hg19: chr4-77420784;