4-76739578-C-A

Variant names:

• chr4-76739578-C-A
• rs344141
• NM_020859.4:c.1405C>A

Variant summary

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

The NM_020859.4(SHROOM3):​c.1405C>A​(p.Pro469Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P469A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: SHROOM3 NM_020859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.33
• Publications: 34 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.

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.1405C>A	p.Pro469Thr	missense	Exon 5 of 11	NP_065910.3	Q8TF72-1
	SHROOM3-AS1	NR_187404.1		n.1044+3230G>T		intron	N/A
	SHROOM3-AS1	NR_187405.1		n.500+3230G>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.1405C>A	p.Pro469Thr	missense	Exon 5 of 11	ENSP00000296043.6	Q8TF72-1
	SHROOM3	ENST00000912766.1		c.1408C>A	p.Pro470Thr	missense	Exon 5 of 11	ENSP00000582825.1
	SHROOM3	ENST00000646790.1		c.1162C>A	p.Pro388Thr	missense	Exon 4 of 10	ENSP00000494970.1	A0A2R8Y5P9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251374 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461878 Hom.: 0 Cov.: 78 AF XY: 0.00000963 AC XY: 7 AN XY: 727234

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.3
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.25		Gain of glycosylation at P469 (P = 0.0222)
MVP		0.25
MPC		0.80
ClinPred		0.94	D
GERP RS		4.6
Varity_R		0.46
gMVP		0.43
Mutation Taster		=86/14	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: rs344141; hg19: chr4-77660731;