1-17826079-G-T

Variant names:

• chr1-17826079-G-T
• rs746694408
• NM_030812.3:c.661G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030812.3(ACTL8):​c.661G>T​(p.Ala221Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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. A221T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACTL8 NM_030812.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.07

Genes affected

ACTL8 (HGNC:24018): (actin like 8) Involved in epithelial cell differentiation. Predicted to be located in cytoplasm. Predicted to be part of dynactin complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.24736822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTL8	NM_030812.3	c.661G>T	p.Ala221Ser	missense_variant	Exon 3 of 3	ENST00000375406.2	NP_110439.2
ACTL8	XM_011542212.3	c.661G>T	p.Ala221Ser	missense_variant	Exon 3 of 3		XP_011540514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTL8	ENST00000375406.2	c.661G>T	p.Ala221Ser	missense_variant	Exon 3 of 3	1	NM_030812.3	ENSP00000364555.1
ACTL8	ENST00000617065.1	c.661G>T	p.Ala221Ser	missense_variant	Exon 2 of 2	2		ENSP00000481590.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455612 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724342

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D;D
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.46	.;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.85	L;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N;.
REVEL	Benign	0.12
Sift	Uncertain	0.0040	D;.
Sift4G	Benign	0.15	T;T
Polyphen		0.60	P;P
Vest4		0.041
MutPred		0.68		Gain of disorder (P = 0.034);Gain of disorder (P = 0.034);
MVP		0.44
MPC		0.45
ClinPred		0.83	D
GERP RS		3.6
Varity_R		0.26
gMVP		0.46

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: rs746694408; hg19: chr1-18152574;