chr12-100220079-C-A

Variant names:

• chr12-100220079-C-A
• rs749116716
• NM_022496.5:c.994C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022496.5(ACTR6):​c.994C>A​(p.Arg332Arg) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACTR6 NM_022496.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.59
• Publications: 1 publications found

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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.11).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022496.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR6	NM_022496.5	MANE Select	c.994C>A	p.Arg332Arg	synonymous	Exon 10 of 11	NP_071941.1	Q9GZN1-1
	ACTR6	NR_048568.2		n.1172C>A		non_coding_transcript_exon	Exon 10 of 11
	ACTR6	NR_048569.2		n.1044C>A		non_coding_transcript_exon	Exon 10 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR6	ENST00000188312.7	TSL:1 MANE Select	c.994C>A	p.Arg332Arg	synonymous	Exon 10 of 11	ENSP00000188312.2	Q9GZN1-1
	ACTR6	ENST00000553038.5	TSL:1	n.*474C>A		non_coding_transcript_exon	Exon 9 of 10	ENSP00000447641.1	F8W043
	ACTR6	ENST00000553038.5	TSL:1	n.*474C>A		3_prime_UTR	Exon 9 of 10	ENSP00000447641.1	F8W043

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.11
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs749116716; hg19: chr12-100613857;