10-102479343-T-G

Variant names:

• chr10-102479343-T-G
• rs5870
• NM_005736.4:c.*1520A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005736.4(ACTR1A):​c.*1520A>C variant causes a 3 prime UTR change involving the alteration of a non-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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACTR1A NM_005736.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.860
• Publications: 31 publications found

Genes affected

ACTR1A (HGNC:167): (actin related protein 1A) This gene encodes a 42.6 kD subunit of dynactin, a macromolecular complex consisting of 10-11 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. It is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit is present in 8-13 copies per dynactin molecule, and is the most abundant molecule in the dynactin complex. It is an actin-related protein, and is approximately 60% identical at the amino acid level to conventional actin. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005736.4. 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
	ACTR1A	NM_005736.4	MANE Select	c.*1520A>C		3_prime_UTR	Exon 11 of 11	NP_005727.1	P61163

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR1A	ENST00000369905.9	TSL:1 MANE Select	c.*1520A>C		3_prime_UTR	Exon 11 of 11	ENSP00000358921.4	P61163
	ACTR1A	ENST00000972053.1		c.*1520A>C		3_prime_UTR	Exon 11 of 11	ENSP00000642112.1
	ACTR1A	ENST00000900302.1		c.*1520A>C		3_prime_UTR	Exon 11 of 11	ENSP00000570361.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 226710 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 123334

African (AFR) AF: 0.00 AC: 0 AN: 5836

American (AMR) AF: 0.00 AC: 0 AN: 12870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4802

East Asian (EAS) AF: 0.00 AC: 0 AN: 8306

South Asian (SAS) AF: 0.00 AC: 0 AN: 44994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 129424

Other (OTH) AF: 0.00 AC: 0 AN: 10462

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 62645

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.67
PhyloP100		0.86

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5870;

hg19: chr10-104239100;