4-76436339-C-T

Variant names:

• chr4-76436339-C-T
• rs554755626
• NM_020859.4:c.168+119C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020859.4(SHROOM3):​c.168+119C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 966,532 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328
• Publications: 0 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
• syndromic disease

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020859.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM3	NM_020859.4	MANE Select	c.168+119C>T		intron	N/A	NP_065910.3	Q8TF72-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM3	ENST00000296043.7	TSL:1 MANE Select	c.168+119C>T		intron	N/A	ENSP00000296043.6	Q8TF72-1
	SHROOM3	ENST00000912766.1		c.168+119C>T		intron	N/A	ENSP00000582825.1
	SHROOM3	ENST00000466541.1	TSL:3	n.75+119C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 2 AN: 966532 Hom.: 0 AF XY: 0.00000202 AC XY: 1 AN XY: 495848

African (AFR) AF: 0.00 AC: 0 AN: 22790

American (AMR) AF: 0.0000287 AC: 1 AN: 34804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20922

East Asian (EAS) AF: 0.00 AC: 0 AN: 36222

South Asian (SAS) AF: 0.00 AC: 0 AN: 67282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3082

European-Non Finnish (NFE) AF: 0.00000144 AC: 1 AN: 693064

Other (OTH) AF: 0.00 AC: 0 AN: 43426

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 71

Bravo AF: 0.148

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.2
DANN	Benign	0.59
PhyloP100		0.33

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

Other links and lift over

dbSNP: rs554755626; hg19: chr4-77357492;