rs61999292

Variant names:

• chr4-76739146-T-G
• rs61999292
• NM_020859.4:c.973T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-76739146-T-G
• chr4-76739146-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020859.4(SHROOM3):​c.973T>G​(p.Ser325Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 1,614,028 control chromosomes in the GnomAD database, including 5,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (371 hom., cov: 33)
  • Exomes 𝑓: 0.080 (5211 hom.)
• Consequence: SHROOM3 NM_020859.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.68
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018060207).
• BP6: Variant 4-76739146-T-G is Benign according to our data. Variant chr4-76739146-T-G is described in ClinVar as Benign. ClinVar VariationId is 403438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0827 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.973T>G	p.Ser325Ala	missense	Exon 5 of 11	NP_065910.3	Q8TF72-1
	SHROOM3-AS1	NR_187404.1		n.1044+3662A>C		intron	N/A
	SHROOM3-AS1	NR_187405.1		n.500+3662A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM3	ENST00000296043.7	TSL:1 MANE Select	c.973T>G	p.Ser325Ala	missense	Exon 5 of 11	ENSP00000296043.6	Q8TF72-1
	SHROOM3	ENST00000912766.1		c.976T>G	p.Ser326Ala	missense	Exon 5 of 11	ENSP00000582825.1
	SHROOM3	ENST00000646790.1		c.730T>G	p.Ser244Ala	missense	Exon 4 of 10	ENSP00000494970.1	A0A2R8Y5P9

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 8877 AN: 152120 Hom.: 372 Cov.: 33

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0413

Gnomad FIN AF: 0.0638

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.0789

GnomAD2 exomes AF: 0.0643 AC: 16146 AN: 251086 AF XY: 0.0658

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.0453

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.000489

Gnomad FIN exome AF: 0.0641

Gnomad NFE exome AF: 0.0887

Gnomad OTH exome AF: 0.0800

GnomAD4 exome AF: 0.0803 AC: 117433 AN: 1461790 Hom.: 5211 Cov.: 76 AF XY: 0.0795 AC XY: 57790 AN XY: 727180

African (AFR) AF: 0.0151 AC: 505 AN: 33478

American (AMR) AF: 0.0486 AC: 2172 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2982 AN: 26136

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39698

South Asian (SAS) AF: 0.0425 AC: 3662 AN: 86256

European-Finnish (FIN) AF: 0.0624 AC: 3333 AN: 53394

Middle Eastern (MID) AF: 0.118 AC: 680 AN: 5768

European-Non Finnish (NFE) AF: 0.0893 AC: 99337 AN: 1111946

Other (OTH) AF: 0.0788 AC: 4756 AN: 60390

GnomAD4 genome AF: 0.0582 AC: 8866 AN: 152238 Hom.: 371 Cov.: 33 AF XY: 0.0566 AC XY: 4213 AN XY: 74452

African (AFR) AF: 0.0152 AC: 631 AN: 41558

American (AMR) AF: 0.0622 AC: 952 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0407 AC: 196 AN: 4818

European-Finnish (FIN) AF: 0.0638 AC: 677 AN: 10608

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0845 AC: 5748 AN: 67988

Other (OTH) AF: 0.0777 AC: 164 AN: 2112

Alfa AF: 0.0766 Hom.: 1151

Bravo AF: 0.0587

TwinsUK AF: 0.0866 AC: 321

ALSPAC AF: 0.0838 AC: 323

ESP6500AA AF: 0.0166 AC: 73

ESP6500EA AF: 0.0929 AC: 799

ExAC AF: 0.0629 AC: 7640

Asia WGS AF: 0.0190 AC: 66 AN: 3478

EpiCase AF: 0.0985

EpiControl AF: 0.103

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	SHROOM3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		2.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.084
Sift	Benign	0.048	D
Sift4G	Benign	0.18	T
Polyphen		0.95	P
Vest4		0.090
MPC		0.35
ClinPred		0.023	T
GERP RS		3.8
Varity_R		0.062
gMVP		0.27
Mutation Taster		=96/4	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: rs61999292; hg19: chr4-77660299; COSMIC: COSV56027088; COSMIC: COSV56027088;