rs201038955

Variant names:

• chr1-17823220-G-A
• rs201038955
• NM_030812.3:c.212G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-17823220-G-A
• chr1-17823220-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030812.3(ACTL8):​c.212G>A​(p.Arg71His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. R71L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ACTL8 NM_030812.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29815656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTL8	NM_030812.3	c.212G>A	p.Arg71His	missense_variant	Exon 2 of 3	ENST00000375406.2	NP_110439.2
ACTL8	XM_011542212.3	c.212G>A	p.Arg71His	missense_variant	Exon 2 of 3		XP_011540514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTL8	ENST00000375406.2	c.212G>A	p.Arg71His	missense_variant	Exon 2 of 3	1	NM_030812.3	ENSP00000364555.1
ACTL8	ENST00000617065.1	c.212G>A	p.Arg71His	missense_variant	Exon 1 of 2	2		ENSP00000481590.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251464 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135910

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: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1461882 Hom.: 0 Cov.: 34 AF XY: 0.0000261 AC XY: 19 AN XY: 727242

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.69	.;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.73	N;.
REVEL	Uncertain	0.31
Sift	Benign	0.071	T;.
Sift4G	Benign	0.14	T;T
Polyphen		0.52	P;P
Vest4		0.14
MVP		0.93
MPC		0.64
ClinPred		0.30	T
GERP RS		1.5
Varity_R		0.11
gMVP		0.61

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: rs201038955; hg19: chr1-18149715; COSMIC: COSV64861125;