4-76519114-T-C

Variant names:

• chr4-76519114-T-C
• rs4371638
• NM_020859.4:c.169-36495T>C

Variant summary

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

The NM_020859.4(SHROOM3):​c.169-36495T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,042 control chromosomes in the GnomAD database, including 30,429 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 0.62 (30429 hom., cov: 33)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

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.169-36495T>C		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.169-36495T>C		intron	N/A	ENSP00000296043.6	Q8TF72-1
	SHROOM3	ENST00000912766.1		c.169-36492T>C		intron	N/A	ENSP00000582825.1
	SHROOM3	ENST00000466541.1	TSL:3	n.76-36495T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93870 AN: 151924 Hom.: 30408 Cov.: 33

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.618 AC: 93935 AN: 152042 Hom.: 30429 Cov.: 33 AF XY: 0.620 AC XY: 46073 AN XY: 74298

African (AFR) AF: 0.820 AC: 34050 AN: 41502

American (AMR) AF: 0.582 AC: 8890 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2408 AN: 3470

East Asian (EAS) AF: 0.575 AC: 2953 AN: 5136

South Asian (SAS) AF: 0.640 AC: 3078 AN: 4812

European-Finnish (FIN) AF: 0.501 AC: 5294 AN: 10560

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 35031 AN: 67970

Other (OTH) AF: 0.645 AC: 1363 AN: 2112

Alfa AF: 0.555 Hom.: 41787

Bravo AF: 0.631

Asia WGS AF: 0.638 AC: 2217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.58
DANN	Benign	0.78
PhyloP100		-1.4
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: rs4371638; hg19: chr4-77440267;