3-169767939-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032487.5(ACTRT3):​c.612C>G​(p.Asp204Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D204G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ACTRT3
NM_032487.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0160
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0805859).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACTRT3NM_032487.5 linkc.612C>G p.Asp204Glu missense_variant Exon 2 of 2 ENST00000330368.3 NP_115876.3 Q9BYD9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACTRT3ENST00000330368.3 linkc.612C>G p.Asp204Glu missense_variant Exon 2 of 2 1 NM_032487.5 ENSP00000333037.1 Q9BYD9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461880
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.612C>G (p.D204E) alteration is located in exon 2 (coding exon 2) of the ACTRT3 gene. This alteration results from a C to G substitution at nucleotide position 612, causing the aspartic acid (D) at amino acid position 204 to be replaced by a glutamic acid (E). 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
0.19
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
9.9
DANN
Benign
0.52
DEOGEN2
Benign
0.15
T
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.49
T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.081
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.45
N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
2.0
N
REVEL
Benign
0.10
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0040
B
Vest4
0.097
MutPred
0.57
Gain of glycosylation at S203 (P = 0.0407);
MVP
0.030
MPC
0.25
ClinPred
0.15
T
GERP RS
4.1
Varity_R
0.046
gMVP
0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1026020120; hg19: chr3-169485727; API