rs377195377

Variant names:

• chr1-17825911-C-G
• rs377195377
• NM_030812.3:c.493C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-17825911-C-G
• chr1-17825911-C-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.493C>G​(p.Pro165Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. P165S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ACTL8 NM_030812.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46

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=0.103288054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTL8	NM_030812.3	c.493C>G	p.Pro165Ala	missense_variant	Exon 3 of 3	ENST00000375406.2	NP_110439.2
ACTL8	XM_011542212.3	c.493C>G	p.Pro165Ala	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.493C>G	p.Pro165Ala	missense_variant	Exon 3 of 3	1	NM_030812.3	ENSP00000364555.1
ACTL8	ENST00000617065.1	c.493C>G	p.Pro165Ala	missense_variant	Exon 2 of 2	2		ENSP00000481590.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249588 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135180

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460682 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726752

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: 0.00000180

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	0.072
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.6
DANN	Benign	0.19
DEOGEN2	Benign	0.39	T;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.47	.;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.10	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.9	N;.
REVEL	Benign	0.16
Sift	Benign	1.0	T;.
Sift4G	Benign	0.78	T;T
Polyphen		0.0050	B;B
Vest4		0.13
MutPred		0.58		Loss of disorder (P = 0.0759);Loss of disorder (P = 0.0759);
MVP		0.36
MPC		0.44
ClinPred		0.15	T
GERP RS		-1.5
Varity_R		0.054
gMVP		0.69

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: rs377195377; hg19: chr1-18152406;