rs774532554

Variant names:

• chr1-3022255-C-A
• rs774532554
• NM_080431.5:c.569C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-3022255-C-A
• chr1-3022255-C-T

Variant summary

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

The NM_080431.5(ACTRT2):​c.569C>A​(p.Thr190Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T190M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ACTRT2 NM_080431.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.07

Genes affected

ACTRT2 (HGNC:24026): (actin related protein T2) The protein encoded by this intronless gene belongs to the actin family. Studies have shown that this protein may be involved in cytoskeletal organization similar to other cytoplasmic actin-related protein (ARP) subfamily members. Antibody raised against the human protein has been used to detect the protein by immunoblotting and immunofluorescence microscopy, demonstrating its specific synthesis in the testis, late in spermatid differentiation, and its localization in the calyx. [provided by RefSeq, Jul 2008]

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, 0.95

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTRT2	NM_080431.5	c.569C>A	p.Thr190Lys	missense_variant	Exon 1 of 1	ENST00000378404.4	NP_536356.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTRT2	ENST00000378404.4	c.569C>A	p.Thr190Lys	missense_variant	Exon 1 of 1	6	NM_080431.5	ENSP00000367658.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000801 AC: 2 AN: 249714 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135386

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

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 AF: 0.00000137 AC: 2 AN: 1460586 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726578

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Pathogenic	4.8	H
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.79		Gain of ubiquitination at T190 (P = 0.023);
MVP		0.44
MPC		0.62
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.95
gMVP		0.96

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: rs774532554; hg19: chr1-2938819;