4-76738783-A-G

Variant names:

• chr4-76738783-A-G
• rs932668101
• NM_020859.4:c.610A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020859.4(SHROOM3):​c.610A>G​(p.Asn204Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N204K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SHROOM3 NM_020859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.44
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09647134).

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.610A>G	p.Asn204Asp	missense	Exon 5 of 11	NP_065910.3	Q8TF72-1
	SHROOM3-AS1	NR_187404.1		n.1044+4025T>C		intron	N/A
	SHROOM3-AS1	NR_187405.1		n.500+4025T>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.610A>G	p.Asn204Asp	missense	Exon 5 of 11	ENSP00000296043.6	Q8TF72-1
	SHROOM3	ENST00000912766.1		c.613A>G	p.Asn205Asp	missense	Exon 5 of 11	ENSP00000582825.1
	SHROOM3	ENST00000646790.1		c.367A>G	p.Asn123Asp	missense	Exon 4 of 10	ENSP00000494970.1	A0A2R8Y5P9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.059
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.12
Sift	Benign	0.041	D
Sift4G	Benign	0.094	T
Polyphen		0.65	P
Vest4		0.093
MutPred		0.077		Gain of phosphorylation at S203 (P = 0.1356)
MVP		0.43
MPC		0.38
ClinPred		0.31	T
GERP RS		4.8
Varity_R		0.13
gMVP		0.088
Mutation Taster		=95/5	polymorphism

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: rs932668101; hg19: chr4-77659936;