chr4-76741156-C-T

Variant names:

• chr4-76741156-C-T
• rs344143
• NM_020859.4:c.2983C>T

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.2983C>T​(p.Leu995Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,572,822 control chromosomes in the GnomAD database, including 160,314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14247 hom., cov: 31)
  • Exomes 𝑓: 0.45 (146067 hom.)
• Consequence: SHROOM3 NM_020859.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0160
• Publications: 9 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=-0.82).
• BP6: Variant 4-76741156-C-T is Benign according to our data. Variant chr4-76741156-C-T is described in ClinVar as Benign. ClinVar VariationId is 403441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.016 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 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.2983C>T	p.Leu995Leu	synonymous	Exon 5 of 11	NP_065910.3	Q8TF72-1
	SHROOM3-AS1	NR_187404.1		n.1044+1652G>A		intron	N/A
	SHROOM3-AS1	NR_187405.1		n.500+1652G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM3	ENST00000296043.7	TSL:1 MANE Select	c.2983C>T	p.Leu995Leu	synonymous	Exon 5 of 11	ENSP00000296043.6	Q8TF72-1
	SHROOM3	ENST00000912766.1		c.2986C>T	p.Leu996Leu	synonymous	Exon 5 of 11	ENSP00000582825.1
	SHROOM3	ENST00000646790.1		c.2740C>T	p.Leu914Leu	synonymous	Exon 4 of 10	ENSP00000494970.1	A0A2R8Y5P9

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65369 AN: 151640 Hom.: 14219 Cov.: 31

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.413

GnomAD2 exomes AF: 0.424 AC: 72525 AN: 170912 AF XY: 0.424

Gnomad AFR exome AF: 0.407

Gnomad AMR exome AF: 0.427

Gnomad ASJ exome AF: 0.400

Gnomad EAS exome AF: 0.255

Gnomad FIN exome AF: 0.437

Gnomad NFE exome AF: 0.466

Gnomad OTH exome AF: 0.425

GnomAD4 exome AF: 0.451 AC: 640618 AN: 1421064 Hom.: 146067 Cov.: 79 AF XY: 0.449 AC XY: 316038 AN XY: 703388

African (AFR) AF: 0.402 AC: 13103 AN: 32580

American (AMR) AF: 0.422 AC: 16196 AN: 38394

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 10045 AN: 25418

East Asian (EAS) AF: 0.245 AC: 9155 AN: 37332

South Asian (SAS) AF: 0.398 AC: 32480 AN: 81594

European-Finnish (FIN) AF: 0.429 AC: 20993 AN: 48908

Middle Eastern (MID) AF: 0.389 AC: 2112 AN: 5436

European-Non Finnish (NFE) AF: 0.468 AC: 511021 AN: 1092540

Other (OTH) AF: 0.433 AC: 25513 AN: 58862

GnomAD4 genome AF: 0.431 AC: 65449 AN: 151758 Hom.: 14247 Cov.: 31 AF XY: 0.427 AC XY: 31645 AN XY: 74150

African (AFR) AF: 0.407 AC: 16868 AN: 41396

American (AMR) AF: 0.421 AC: 6424 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1372 AN: 3468

East Asian (EAS) AF: 0.251 AC: 1275 AN: 5080

South Asian (SAS) AF: 0.385 AC: 1856 AN: 4818

European-Finnish (FIN) AF: 0.435 AC: 4588 AN: 10550

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.464 AC: 31496 AN: 67854

Other (OTH) AF: 0.412 AC: 872 AN: 2114

Alfa AF: 0.454 Hom.: 4985

Bravo AF: 0.429

Asia WGS AF: 0.328 AC: 1142 AN: 3478

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	-0.82
CADD	Benign	5.3
DANN	Benign	0.67
PhyloP100		0.016
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: rs344143; hg19: chr4-77662309; COSMIC: COSV56022693; COSMIC: COSV56022693;