rs145112769

Variant names:

• chr4-76730904-G-C
• rs145112769
• NM_020859.4:c.556G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-76730904-G-C
• chr4-76730904-G-A
• chr4-76730904-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_020859.4(SHROOM3):​c.556G>C​(p.Gly186Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,614,090 control chromosomes in the GnomAD database, including 160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0015 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (151 hom.)
• Consequence: SHROOM3 NM_020859.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.82
• Publications: 5 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029561818).
• BP6: Variant 4-76730904-G-C is Benign according to our data. Variant chr4-76730904-G-C is described in ClinVar as Benign. ClinVar VariationId is 3038663.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00154 (234/152222) while in subpopulation SAS AF = 0.0473 (228/4816). AF 95% confidence interval is 0.0423. There are 9 homozygotes in GnomAd4. There are 176 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 234 AD gene.

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.556G>C	p.Gly186Arg	missense	Exon 4 of 11	NP_065910.3	Q8TF72-1
	SHROOM3-AS1	NR_187404.1		n.1044+11904C>G		intron	N/A
	SHROOM3-AS1	NR_187405.1		n.500+11904C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM3	ENST00000296043.7	TSL:1 MANE Select	c.556G>C	p.Gly186Arg	missense	Exon 4 of 11	ENSP00000296043.6	Q8TF72-1
	SHROOM3	ENST00000912766.1		c.559G>C	p.Gly187Arg	missense	Exon 4 of 11	ENSP00000582825.1
	SHROOM3	ENST00000646790.1		c.313G>C	p.Gly105Arg	missense	Exon 3 of 10	ENSP00000494970.1	A0A2R8Y5P9

Frequencies

GnomAD3 genomes AF: 0.00155 AC: 236 AN: 152104 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0477

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00632 AC: 1589 AN: 251478 AF XY: 0.00867

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00309

GnomAD4 exome AF: 0.00313 AC: 4578 AN: 1461868 Hom.: 151 Cov.: 30 AF XY: 0.00465 AC XY: 3382 AN XY: 727242

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0501 AC: 4320 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.0000638 AC: 71 AN: 1112002

Other (OTH) AF: 0.00278 AC: 168 AN: 60394

GnomAD4 genome AF: 0.00154 AC: 234 AN: 152222 Hom.: 9 Cov.: 32 AF XY: 0.00236 AC XY: 176 AN XY: 74420

African (AFR) AF: 0.0000963 AC: 4 AN: 41538

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.0473 AC: 228 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000305 Hom.: 2

Bravo AF: 0.000382

ExAC AF: 0.00727 AC: 883

Asia WGS AF: 0.0180 AC: 61 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SHROOM3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.8
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.049	D
Polyphen		0.99	D
Vest4		0.80
MVP		0.57
MPC		1.1
ClinPred		0.11	T
GERP RS		4.9
Varity_R		0.38
gMVP		0.38
Mutation Taster		=95/5	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: rs145112769; hg19: chr4-77652057;