rs376510300

Variant names:

• chr1-236686786-A-C
• NM_001103.4:c.113A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-236686786-A-C
• chr1-236686786-A-G

Variant summary

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

The NM_001103.4(ACTN2):​c.113A>C​(p.Lys38Thr) variant causes a missense change involving the alteration of a conserved nucleotide. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K38R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ACTN2 NM_001103.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.43

Genes affected

ACTN2 (HGNC:164): (actinin alpha 2) Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. This gene encodes a muscle-specific, alpha actinin isoform that is expressed in both skeletal and cardiac muscles. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]

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=0.38627872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTN2	NM_001103.4	c.113A>C	p.Lys38Thr	missense_variant	Exon 1 of 21	ENST00000366578.6	NP_001094.1
ACTN2	NM_001278343.2	c.113A>C	p.Lys38Thr	missense_variant	Exon 1 of 21		NP_001265272.1
ACTN2	NR_184402.1	n.288A>C		non_coding_transcript_exon_variant	Exon 1 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTN2	ENST00000366578.6	c.113A>C	p.Lys38Thr	missense_variant	Exon 1 of 21	1	NM_001103.4	ENSP00000355537.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	.;D
Eigen	Benign	-0.095
Eigen_PC	Benign	0.024
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.26
Sift	Benign	0.032	D;D
Sift4G	Benign	0.20	T;T
Polyphen		0.010	.;B
Vest4		0.48
MutPred		0.42		Loss of methylation at K38 (P = 0.0171);Loss of methylation at K38 (P = 0.0171);
MVP		0.73
MPC		1.0
ClinPred		0.95	D
GERP RS		3.6
Varity_R		0.86
gMVP		0.66

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.

Other links and lift over

hg19: chr1-236850086;