7-152783233-A-T

Position:

• chr7-152783233-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020445.6(ACTR3B):​c.91A>T​(p.Ile31Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ACTR3B NM_020445.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.22

Genes affected

ACTR3B (HGNC:17256): (actin related protein 3B) This gene encodes a member of the actin-related proteins (ARP), which form multiprotein complexes and share 35-55% amino acid identity with conventional actin. The protein encoded by this gene may have a regulatory role in the actin cytoskeleton and induce cell-shape change and motility. Pseudogenes of this gene are located on chromosomes 2, 4, 10, 16, 22 and Y. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jul 2012]

ACTR3B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR3B	NM_020445.6	c.91A>T	p.Ile31Phe	missense_variant	2/12	ENST00000256001.13	NP_065178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTR3B	ENST00000256001.13	c.91A>T	p.Ile31Phe	missense_variant	2/12	1	NM_020445.6	ENSP00000256001.8
ACTR3B	ENST00000377776.7	c.91A>T	p.Ile31Phe	missense_variant	2/10	1		ENSP00000367007.3
ACTR3B	ENST00000397282.2	c.-164-17298A>T		intron_variant		2		ENSP00000380452.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 20

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.91A>T (p.I31F) alteration is located in exon 2 (coding exon 2) of the ACTR3B gene. This alteration results from a A to T substitution at nucleotide position 91, causing the isoleucine (I) at amino acid position 31 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	23
DANN	Benign	0.91
DEOGEN2	Benign	0.39	.;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	-0.020	N;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.46	N;N
REVEL	Uncertain	0.53
Sift	Benign	0.81	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.058	B;B
Vest4		0.78
MutPred		0.74		Loss of catalytic residue at S33 (P = 0.1443);Loss of catalytic residue at S33 (P = 0.1443);
MVP		0.90
MPC		1.8
ClinPred		0.60	D
GERP RS		3.6
Varity_R		0.070
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-152480318;