3-169767599-C-A

Variant names:

• chr3-169767599-C-A
• rs1202342289
• NM_032487.5:c.952G>T

Variant summary

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

The NM_032487.5(ACTRT3):​c.952G>T​(p.Ala318Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACTRT3 NM_032487.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.16

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 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 rank	MANE	Protein	UniProt
ACTRT3	NM_032487.5	c.952G>T	p.Ala318Ser	missense_variant	Exon 2 of 2	ENST00000330368.3	NP_115876.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTRT3	ENST00000330368.3	c.952G>T	p.Ala318Ser	missense_variant	Exon 2 of 2	1	NM_032487.5	ENSP00000333037.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251308 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135818

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.952G>T (p.A318S) alteration is located in exon 2 (coding exon 2) of the ACTRT3 gene. This alteration results from a G to T substitution at nucleotide position 952, causing the alanine (A) at amino acid position 318 to be replaced by a serine (S). 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	0.16
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.045
Eigen_PC	Benign	-0.069
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Uncertain	2.0	M
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.39
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.067	T
Polyphen		0.22	B
Vest4		0.15
MutPred		0.76		Loss of methylation at K316 (P = 0.0994);
MVP		0.28
MPC		0.31
ClinPred		0.88	D
GERP RS		4.3
Varity_R		0.28
gMVP		0.17

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

Other links and lift over

dbSNP: rs1202342289; hg19: chr3-169485387;