chr3-169767856-C-T

Variant names:

• chr3-169767856-C-T
• NM_032487.5:c.695G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032487.5(ACTRT3):​c.695G>A​(p.Cys232Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACTRT3 NM_032487.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.38
• Publications: 0 publications found

Genes affected

ACTRT3 (HGNC:24022): (actin related protein T3) Predicted to be located in male germ cell nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060153037).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032487.5. 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
	ACTRT3	NM_032487.5	MANE Select	c.695G>A	p.Cys232Tyr	missense	Exon 2 of 2	NP_115876.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTRT3	ENST00000330368.3	TSL:1 MANE Select	c.695G>A	p.Cys232Tyr	missense	Exon 2 of 2	ENSP00000333037.1	Q9BYD9
	ACTRT3	ENST00000956146.1		c.695G>A	p.Cys232Tyr	missense	Exon 2 of 3	ENSP00000626205.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.029
DANN	Benign	0.48
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.4
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.19
Sift	Benign	0.030	D
Sift4G	Uncertain	0.010	D
Polyphen		0.0	B
Vest4		0.051
MutPred		0.37		Loss of catalytic residue at L233 (P = 0.0102)
MVP		0.076
MPC		0.43
ClinPred		0.064	T
GERP RS		-8.3
Varity_R		0.12
gMVP		0.37
Mutation Taster		=99/1	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

hg19: chr3-169485644; COSMIC: COSV57754046; COSMIC: COSV57754046;