20-36793416-G-A

Variant names:

• chr20-36793416-G-A
• rs564328004
• NM_080627.4:c.4666C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080627.4(MTCL2):​c.4666C>T​(p.Pro1556Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1556A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTCL2 NM_080627.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.106297284).

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.4666C>T	p.Pro1556Ser	missense	Exon 14 of 15	NP_542194.2	O94964-2
	MTCL2	NM_199181.3		c.2993+959C>T		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.4666C>T	p.Pro1556Ser	missense	Exon 14 of 15	ENSP00000237536.4	O94964-2
	MTCL2	ENST00000938705.1		c.4603C>T	p.Pro1535Ser	missense	Exon 13 of 14	ENSP00000608764.1
	MTCL2	ENST00000279034.10	TSL:5	c.2993+959C>T		intron	N/A	ENSP00000279034.5	X6R3R3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.81
Eigen	Benign	0.015
Eigen_PC	Benign	0.095
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.1
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.032
Sift	Benign	0.71	T
Sift4G	Benign	0.85	T
Vest4		0.13
MutPred		0.17		Gain of phosphorylation at P1556 (P = 0.0092)
MVP		0.12
MPC		1.1
ClinPred		0.14	T
GERP RS		3.9
gMVP		0.13
Mutation Taster		=88/12	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: rs564328004; hg19: chr20-35421819;