1-25446797-C-G

Position:

• chr1-25446797-C-G

Variant summary

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

The NM_018202.6(MACO1):​c.116C>G​(p.Ala39Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MACO1 NM_018202.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62

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 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=0.32124054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACO1	NM_018202.6	c.116C>G	p.Ala39Gly	missense_variant	2/11	ENST00000374343.5	NP_060672.2
MACO1	NM_001282564.2	c.116C>G	p.Ala39Gly	missense_variant	2/9		NP_001269493.1
MACO1	XM_005245931.3	c.116C>G	p.Ala39Gly	missense_variant	2/10		XP_005245988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACO1	ENST00000374343.5	c.116C>G	p.Ala39Gly	missense_variant	2/11	1	NM_018202.6	ENSP00000363463.4
MACO1	ENST00000399766.7	c.116C>G	p.Ala39Gly	missense_variant	2/9	1		ENSP00000382668.3
MACO1	ENST00000647928.1	n.116C>G		non_coding_transcript_exon_variant	2/11			ENSP00000497738.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2024

The c.116C>G (p.A39G) alteration is located in exon 2 (coding exon 2) of the TMEM57 gene. This alteration results from a C to G substitution at nucleotide position 116, causing the alanine (A) at amino acid position 39 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	.;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	1.3	L;L
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.53
Sift	Benign	0.096	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.99	D;B
Vest4		0.42
MutPred		0.72		Loss of helix (P = 0.0795);Loss of helix (P = 0.0795);
MVP		0.36
MPC		1.3
ClinPred		0.86	D
GERP RS		5.9
Varity_R		0.39
gMVP		0.67

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: chr1-25773288;