3-169767817-A-G

Position:

• chr3-169767817-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_032487.5(ACTRT3):​c.734T>C​(p.Ile245Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.39

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.947

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTRT3	NM_032487.5	c.734T>C	p.Ile245Thr	missense_variant	2/2	ENST00000330368.3	NP_115876.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTRT3	ENST00000330368.3	c.734T>C	p.Ile245Thr	missense_variant	2/2	1	NM_032487.5	ENSP00000333037.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jul 28, 2021

The c.734T>C (p.I245T) alteration is located in exon 2 (coding exon 2) of the ACTRT3 gene. This alteration results from a T to C substitution at nucleotide position 734, causing the isoleucine (I) at amino acid position 245 to be replaced by a threonine (T). 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	Pathogenic	0.62
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.95	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Pathogenic	3.9	H
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.076	B
Vest4		0.56
MutPred		0.77		Gain of disorder (P = 0.037);
MVP		0.30
MPC		0.77
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.44
gMVP		0.52

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-169485605;