20-36793674-C-T

Variant names:

• chr20-36793674-C-T
• rs868239780
• NM_080627.4:c.4408G>A

Variant summary

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

The NM_080627.4(MTCL2):​c.4408G>A​(p.Gly1470Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,397,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: MTCL2 NM_080627.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05
• Publications: 0 publications found

Genes affected

MTCL2 (HGNC:16111): (microtubule crosslinking factor 2) Predicted to be involved in insulin receptor signaling pathway; negative regulation of gluconeogenesis; and regulation of autophagy. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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=0.32238704).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080627.4. 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
	MTCL2	NM_080627.4	MANE Select	c.4408G>A	p.Gly1470Ser	missense	Exon 14 of 15	NP_542194.2	O94964-2
	MTCL2	NM_199181.3		c.2993+701G>A		intron	N/A	NP_954650.2	X6R3R3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTCL2	ENST00000237536.9	TSL:5 MANE Select	c.4408G>A	p.Gly1470Ser	missense	Exon 14 of 15	ENSP00000237536.4	O94964-2
	MTCL2	ENST00000938705.1		c.4345G>A	p.Gly1449Ser	missense	Exon 13 of 14	ENSP00000608764.1
	MTCL2	ENST00000279034.10	TSL:5	c.2993+701G>A		intron	N/A	ENSP00000279034.5	X6R3R3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000263 AC: 4 AN: 152174 AF XY: 0.0000247

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000919

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000507

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000930 AC: 13 AN: 1397720 Hom.: 0 Cov.: 30 AF XY: 0.0000131 AC XY: 9 AN XY: 689452

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35738

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000834 AC: 9 AN: 1078954

Other (OTH) AF: 0.0000172 AC: 1 AN: 57982

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000358 Hom.: 0

Bravo AF: 0.0000151

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	Benign	0.17
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	27
DANN	Benign	0.96
Eigen	Benign	-0.086
Eigen_PC	Benign	-0.090
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.1
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.19
Sift	Benign	0.15	T
Sift4G	Benign	0.44	T
Vest4		0.58
MutPred		0.15		Gain of phosphorylation at G1470 (P = 0.0797)
MVP		0.10
MPC		2.2
ClinPred		0.23	T
GERP RS		3.9
gMVP		0.35
Mutation Taster		=58/42	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

dbSNP: rs868239780; hg19: chr20-35422077;