rs344135

Variant names:

• chr4-76731066-T-C
• rs344135
• NM_020859.4:c.587+131T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-76731066-T-C
• chr4-76731066-T-G

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.587+131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,233,154 control chromosomes in the GnomAD database, including 95,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9045 hom., cov: 32)
  • Exomes 𝑓: 0.38 (86703 hom.)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.792
• Publications: 2 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 (BayesDel_noAF=-0.9).
• BP6: Variant 4-76731066-T-C is Benign according to our data. Variant chr4-76731066-T-C is described in ClinVar as Benign. ClinVar VariationId is 1236225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.416 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.587+131T>C		intron	N/A	NP_065910.3
	SHROOM3-AS1	NR_187404.1		n.1044+11742A>G		intron	N/A
	SHROOM3-AS1	NR_187405.1		n.500+11742A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM3	ENST00000296043.7	TSL:1 MANE Select	c.587+131T>C		intron	N/A	ENSP00000296043.6
	SHROOM3	ENST00000646790.1		c.344+131T>C		intron	N/A	ENSP00000494970.1
	SHROOM3	ENST00000469923.5	TSL:3	n.414+131T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48601 AN: 151996 Hom.: 9040 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.384 AC: 415240 AN: 1081040 Hom.: 86703 AF XY: 0.381 AC XY: 210616 AN XY: 552906

African (AFR) AF: 0.148 AC: 3834 AN: 25894

American (AMR) AF: 0.310 AC: 12425 AN: 40032

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 12553 AN: 22794

East Asian (EAS) AF: 0.0134 AC: 480 AN: 35934

South Asian (SAS) AF: 0.247 AC: 18956 AN: 76670

European-Finnish (FIN) AF: 0.346 AC: 12604 AN: 36448

Middle Eastern (MID) AF: 0.403 AC: 1965 AN: 4872

European-Non Finnish (NFE) AF: 0.423 AC: 334794 AN: 791166

Other (OTH) AF: 0.373 AC: 17629 AN: 47230

GnomAD4 genome AF: 0.320 AC: 48616 AN: 152114 Hom.: 9045 Cov.: 32 AF XY: 0.315 AC XY: 23394 AN XY: 74370

African (AFR) AF: 0.158 AC: 6567 AN: 41502

American (AMR) AF: 0.342 AC: 5228 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1887 AN: 3470

East Asian (EAS) AF: 0.0283 AC: 147 AN: 5186

South Asian (SAS) AF: 0.241 AC: 1162 AN: 4828

European-Finnish (FIN) AF: 0.354 AC: 3742 AN: 10564

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28587 AN: 67972

Other (OTH) AF: 0.350 AC: 738 AN: 2110

Alfa AF: 0.393 Hom.: 52991

Bravo AF: 0.315

Asia WGS AF: 0.139 AC: 486 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.88
DANN	Benign	0.36
PhyloP100		-0.79
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: rs344135; hg19: chr4-77652219;