rs10903129

Positions:

• chr1-25442446-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018202.6(MACO1):​c.81-4316A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,980 control chromosomes in the GnomAD database, including 25,592 homozygotes. 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: 𝑓 0.57 (25592 hom., cov: 31)
• Consequence: MACO1 NM_018202.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.783

Genes affected

MACO1 (HGNC:25572): (macoilin 1) Predicted to enable actin filament binding activity and microtubule binding activity. Involved in neuronal signal transduction. Located in rough endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACO1	NM_018202.6	c.81-4316A>G		intron_variant		ENST00000374343.5	NP_060672.2
MACO1	NM_001282564.2	c.81-4316A>G		intron_variant			NP_001269493.1
MACO1	XM_005245931.3	c.81-4316A>G		intron_variant			XP_005245988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACO1	ENST00000374343.5	c.81-4316A>G		intron_variant		1	NM_018202.6	ENSP00000363463	P1
MACO1	ENST00000399766.7	c.81-4316A>G		intron_variant		1		ENSP00000382668
MACO1	ENST00000647928.1	c.81-4316A>G		intron_variant, NMD_transcript_variant				ENSP00000497738

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86452 AN: 151862 Hom.: 25541 Cov.: 31

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.538

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.569 AC: 86549 AN: 151980 Hom.: 25592 Cov.: 31 AF XY: 0.563 AC XY: 41780 AN XY: 74272

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.533

Alfa AF: 0.534 Hom.: 51141

Bravo AF: 0.578

Asia WGS AF: 0.306 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	10
DANN	Benign	0.79

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: rs10903129; hg19: chr1-25768937;