Variant 12-100212295-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_022496.5(ACTR6):c.612A>C(p.Gln204His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ACTR6
NM_022496.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

Variant links:

Genes affected

ACTR6 (HGNC:24025): (actin related protein 6) Predicted to enable nucleosome binding activity. Predicted to be involved in histone exchange. Predicted to be located in nucleus. Predicted to be part of Swr1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACTR6 links:

ACTR6 (HGNC:):

ACTR6 links:

DEPDC4 (HGNC:22952): (DEP domain containing 4) Predicted to be involved in intracellular signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

DEPDC4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.777

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR6	NM_022496.5 linkuse as main transcript	c.612A>C	p.Gln204His	missense_variant	7/11	ENST00000188312.7	NP_071941.1	Q9GZN1-1
ACTR6	NR_048568.2 linkuse as main transcript	n.790A>C		non_coding_transcript_exon_variant	7/11
ACTR6	NR_048569.2 linkuse as main transcript	n.662A>C		non_coding_transcript_exon_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTR6	ENST00000188312.7 linkuse as main transcript	c.612A>C	p.Gln204His	missense_variant	7/11	1	NM_022496.5	ENSP00000188312.2		Q9GZN1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459874

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726130

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2023

The c.612A>C (p.Q204H) alteration is located in exon 7 (coding exon 7) of the ACTR6 gene. This alteration results from a A to C substitution at nucleotide position 612, causing the glutamine (Q) at amino acid position 204 to be replaced by a histidine (H). 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

0.93

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.79

D;D;.;D

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.78

D;D;D;D

MetaSVM

Uncertain

0.76

MutationAssessor

Benign

2.0

M;.;.;.

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-4.6

D;D;D;D

REVEL

Pathogenic

0.85

Sift

Benign

0.11

T;D;T;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.63

MutPred

0.60

Loss of catalytic residue at Q204 (P = 0.0624);.;Loss of catalytic residue at Q204 (P = 0.0624);.;

MVP

0.93

MPC

1.3

ClinPred

0.99

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.72

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over