chr4-76741095-G-A

Variant names:

• chr4-76741095-G-A
• rs344142
• NM_020859.4:c.2922G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020859.4(SHROOM3):​c.2922G>A​(p.Ser974Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,544,448 control chromosomes in the GnomAD database, including 265,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (22207 hom., cov: 31)
  • Exomes 𝑓: 0.58 (242881 hom.)
• Consequence: SHROOM3 NM_020859.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.00
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-76741095-G-A is Benign according to our data. Variant chr4-76741095-G-A is described in ClinVar as Benign. ClinVar VariationId is 403440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.606 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.2922G>A	p.Ser974Ser	synonymous	Exon 5 of 11	NP_065910.3	Q8TF72-1
	SHROOM3-AS1	NR_187404.1		n.1044+1713C>T		intron	N/A
	SHROOM3-AS1	NR_187405.1		n.500+1713C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM3	ENST00000296043.7	TSL:1 MANE Select	c.2922G>A	p.Ser974Ser	synonymous	Exon 5 of 11	ENSP00000296043.6	Q8TF72-1
	SHROOM3	ENST00000912766.1		c.2925G>A	p.Ser975Ser	synonymous	Exon 5 of 11	ENSP00000582825.1
	SHROOM3	ENST00000646790.1		c.2679G>A	p.Ser893Ser	synonymous	Exon 4 of 10	ENSP00000494970.1	A0A2R8Y5P9

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80595 AN: 151750 Hom.: 22183 Cov.: 31

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.540

GnomAD2 exomes AF: 0.533 AC: 73212 AN: 137298 AF XY: 0.530

Gnomad AFR exome AF: 0.424

Gnomad AMR exome AF: 0.515

Gnomad ASJ exome AF: 0.648

Gnomad EAS exome AF: 0.258

Gnomad FIN exome AF: 0.576

Gnomad NFE exome AF: 0.619

Gnomad OTH exome AF: 0.573

GnomAD4 exome AF: 0.585 AC: 814551 AN: 1392582 Hom.: 242881 Cov.: 78 AF XY: 0.582 AC XY: 399681 AN XY: 686732

African (AFR) AF: 0.413 AC: 12927 AN: 31282

American (AMR) AF: 0.512 AC: 17964 AN: 35070

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 16041 AN: 24834

East Asian (EAS) AF: 0.246 AC: 8732 AN: 35544

South Asian (SAS) AF: 0.446 AC: 35198 AN: 78904

European-Finnish (FIN) AF: 0.568 AC: 26526 AN: 46734

Middle Eastern (MID) AF: 0.539 AC: 2966 AN: 5506

European-Non Finnish (NFE) AF: 0.614 AC: 661734 AN: 1077014

Other (OTH) AF: 0.563 AC: 32463 AN: 57694

GnomAD4 genome AF: 0.531 AC: 80672 AN: 151866 Hom.: 22207 Cov.: 31 AF XY: 0.525 AC XY: 38994 AN XY: 74218

African (AFR) AF: 0.420 AC: 17418 AN: 41468

American (AMR) AF: 0.530 AC: 8099 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2229 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1286 AN: 5098

South Asian (SAS) AF: 0.428 AC: 2065 AN: 4820

European-Finnish (FIN) AF: 0.578 AC: 6100 AN: 10558

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.611 AC: 41464 AN: 67860

Other (OTH) AF: 0.538 AC: 1137 AN: 2114

Alfa AF: 0.579 Hom.: 5393

Bravo AF: 0.526

Asia WGS AF: 0.350 AC: 1218 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	SHROOM3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.62
PhyloP100		-1.0
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: rs344142; hg19: chr4-77662248; COSMIC: COSV56022679; COSMIC: COSV56022679;