6-127476312-G-C

Variant names:

• chr6-127476312-G-C
• NM_001400265.1:c.1714C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001400265.1(MTCL3):​c.1714C>G​(p.Pro572Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MTCL3 NM_001400265.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.95
• Publications: 0 publications found

Genes affected

MTCL3 (HGNC:21494): (MTCL family member 3) Predicted to be involved in regulation of autophagy. Predicted to be located in extracellular space. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255330 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32142913).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400265.1. 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
	MTCL3	NM_001400265.1	MANE Select	c.1714C>G	p.Pro572Ala	missense	Exon 6 of 7	NP_001387194.1	Q5TF21
	SOGA3-KIAA0408	NR_174482.1		n.2559C>G		non_coding_transcript_exon	Exon 6 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTCL3	ENST00000525778.6	TSL:5 MANE Select	c.1714C>G	p.Pro572Ala	missense	Exon 6 of 7	ENSP00000434570.1	Q5TF21
	ENSG00000255330	ENST00000481848.6	TSL:5	n.1714C>G		non_coding_transcript_exon	Exon 6 of 12	ENSP00000455908.1
	MTCL3	ENST00000465909.3	TSL:5	c.1714C>G	p.Pro572Ala	missense	Exon 6 of 7	ENSP00000435559.1	E9PJP2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.0070	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.9
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.27
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.48
MutPred		0.15		Loss of glycosylation at P572 (P = 0.1117)
MVP		0.17
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.34
gMVP		0.62
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

hg19: chr6-127797457;