rs564328004

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-36793416-G-A
• chr20-36793416-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/18 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

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

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=0.106297284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTCL2	NM_080627.4	c.4666C>T	p.Pro1556Ser	missense_variant	Exon 14 of 15	ENST00000237536.9	NP_542194.2
MTCL2	NM_199181.3	c.2993+959C>T		intron_variant	Intron 14 of 14		NP_954650.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOGA1	ENST00000237536.9	c.4666C>T	p.Pro1556Ser	missense_variant	Exon 14 of 15	5	NM_080627.4	ENSP00000237536.4
SOGA1	ENST00000279034.10	c.2993+959C>T		intron_variant	Intron 14 of 14	5		ENSP00000279034.5
SOGA1	ENST00000465671.1	n.3505C>T		non_coding_transcript_exon_variant	Exon 10 of 12	2		ENSP00000433939.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
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

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

LitVar

Other links and lift over

dbSNP: rs564328004; hg19: chr20-35421819;