4-76770561-G-A

Variant names:

• chr4-76770561-G-A
• rs7676973
• NM_020859.4:c.5350-65G>A

Variant summary

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

The NM_020859.4(SHROOM3):​c.5350-65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 1,595,528 control chromosomes in the GnomAD database, including 3,380 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 0.059 (292 hom., cov: 31)
  • Exomes 𝑓: 0.062 (3088 hom.)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• Publications: 3 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-AS1 (HGNC:41265): (SHROOM3 antisense RNA 1)

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 (NFE) allele frequency at 95% confidence interval = 0.069 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM3	NM_020859.4	MANE Select	c.5350-65G>A		intron	N/A	NP_065910.3
	SHROOM3-AS1	NR_187404.1		n.408-11969C>T		intron	N/A
	SHROOM3-AS1	NR_187405.1		n.408-27661C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM3	ENST00000296043.7	TSL:1 MANE Select	c.5350-65G>A		intron	N/A	ENSP00000296043.6
	SHROOM3	ENST00000646790.1		c.5107-65G>A		intron	N/A	ENSP00000494970.1
	SHROOM3-AS1	ENST00000449007.2	TSL:3	n.85-11969C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0590 AC: 8968 AN: 151932 Hom.: 293 Cov.: 31

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.00483

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0707

Gnomad OTH AF: 0.0561

GnomAD4 exome AF: 0.0616 AC: 88941 AN: 1443478 Hom.: 3088 AF XY: 0.0605 AC XY: 43418 AN XY: 718068

African (AFR) AF: 0.0565 AC: 1878 AN: 33252

American (AMR) AF: 0.0345 AC: 1516 AN: 43926

Ashkenazi Jewish (ASJ) AF: 0.0348 AC: 905 AN: 25998

East Asian (EAS) AF: 0.00804 AC: 318 AN: 39566

South Asian (SAS) AF: 0.0163 AC: 1387 AN: 85162

European-Finnish (FIN) AF: 0.0674 AC: 3187 AN: 47262

Middle Eastern (MID) AF: 0.0316 AC: 139 AN: 4404

European-Non Finnish (NFE) AF: 0.0691 AC: 76293 AN: 1104086

Other (OTH) AF: 0.0555 AC: 3318 AN: 59822

GnomAD4 genome AF: 0.0590 AC: 8974 AN: 152050 Hom.: 292 Cov.: 31 AF XY: 0.0577 AC XY: 4290 AN XY: 74332

African (AFR) AF: 0.0557 AC: 2310 AN: 41488

American (AMR) AF: 0.0415 AC: 633 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3472

East Asian (EAS) AF: 0.00484 AC: 25 AN: 5162

South Asian (SAS) AF: 0.0129 AC: 62 AN: 4810

European-Finnish (FIN) AF: 0.0733 AC: 776 AN: 10582

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0707 AC: 4805 AN: 67954

Other (OTH) AF: 0.0556 AC: 117 AN: 2106

Alfa AF: 0.0702 Hom.: 63

Bravo AF: 0.0565

Asia WGS AF: 0.0120 AC: 41 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	0.13
DANN	Benign	0.41
PhyloP100		-0.57
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: rs7676973; hg19: chr4-77691714;