rs1080708

Variant names:

• chr6-127489220-T-G
• rs1080708
• NM_001400265.1:c.1486-6236A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001400265.1(MTCL3):​c.1486-6236A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,926 control chromosomes in the GnomAD database, including 32,989 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 0.66 (32989 hom., cov: 31)
• Consequence: MTCL3 NM_001400265.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTCL3	NM_001400265.1	MANE Select	c.1486-6236A>C		intron	N/A	NP_001387194.1
	SOGA3-KIAA0408	NR_174482.1		n.2331-6236A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTCL3	ENST00000525778.6	TSL:5 MANE Select	c.1486-6236A>C		intron	N/A	ENSP00000434570.1
	ENSG00000255330	ENST00000481848.6	TSL:5	n.1486-6236A>C		intron	N/A	ENSP00000455908.1
	MTCL3	ENST00000465909.3	TSL:5	c.1486-6236A>C		intron	N/A	ENSP00000435559.1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99684 AN: 151808 Hom.: 32947 Cov.: 31

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.657 AC: 99786 AN: 151926 Hom.: 32989 Cov.: 31 AF XY: 0.653 AC XY: 48472 AN XY: 74248

African (AFR) AF: 0.709 AC: 29378 AN: 41440

American (AMR) AF: 0.683 AC: 10442 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2103 AN: 3470

East Asian (EAS) AF: 0.740 AC: 3804 AN: 5140

South Asian (SAS) AF: 0.521 AC: 2508 AN: 4814

European-Finnish (FIN) AF: 0.603 AC: 6351 AN: 10532

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.635 AC: 43154 AN: 67940

Other (OTH) AF: 0.645 AC: 1359 AN: 2108

Alfa AF: 0.656 Hom.: 5547

Bravo AF: 0.669

Asia WGS AF: 0.616 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.57
DANN	Benign	0.47
PhyloP100		-0.97

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

dbSNP: rs1080708; hg19: chr6-127810365; COSMIC: COSV64105769;