1-25458718-G-T

Position:

• chr1-25458718-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018202.6(MACO1):​c.980G>T​(p.Gly327Val) 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: 5.47

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.181279).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACO1	NM_018202.6	c.980G>T	p.Gly327Val	missense_variant	6/11	ENST00000374343.5	NP_060672.2
MACO1	XM_005245931.3	c.980G>T	p.Gly327Val	missense_variant	6/10		XP_005245988.1
MACO1	NM_001282564.2	c.473+4336G>T		intron_variant			NP_001269493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACO1	ENST00000374343.5	c.980G>T	p.Gly327Val	missense_variant	6/11	1	NM_018202.6	ENSP00000363463.4
MACO1	ENST00000399766.7	c.473+4336G>T		intron_variant		1		ENSP00000382668.3
MACO1	ENST00000470035.1	n.494G>T		non_coding_transcript_exon_variant	3/3	3
MACO1	ENST00000647928.1	n.980G>T		non_coding_transcript_exon_variant	6/11			ENSP00000497738.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Mar 21, 2024

The c.980G>T (p.G327V) alteration is located in exon 6 (coding exon 6) of the TMEM57 gene. This alteration results from a G to T substitution at nucleotide position 980, causing the glycine (G) at amino acid position 327 to be replaced by a valine (V). 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	0.085
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.081
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.048	D
Polyphen		0.21	B
Vest4		0.18
MutPred		0.39		Loss of glycosylation at S326 (P = 0.032);
MVP		0.043
MPC		0.15
ClinPred		0.76	D
GERP RS		5.8
Varity_R		0.36
gMVP		0.80

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: chr1-25785209;