18-8706591-C-T

Variant names:

• chr18-8706591-C-T
• rs1408233142
• NM_001395333.1:c.931C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001395333.1(MTCL1):​c.931C>T​(p.Pro311Ser) 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. 10/13 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. P311A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MTCL1 NM_001395333.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 0 publications found

Genes affected

MTCL1 (HGNC:29121): (microtubule crosslinking factor 1) Enables microtubule binding activity. Predicted to be involved in establishment or maintenance of epithelial cell apical/basal polarity; microtubule bundle formation; and positive regulation of protein targeting to membrane. Located in midbody and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

GACAT2 (HGNC:50516): (gastric cancer associated transcript 2)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04716721).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395333.1. 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
	MTCL1	NM_001395333.1	MANE Select	c.931C>T	p.Pro311Ser	missense	Exon 1 of 15	NP_001382262.1	A0A8Q3WKN6
	MTCL1	NM_001378207.1		c.931C>T	p.Pro311Ser	missense	Exon 1 of 14	NP_001365136.1	A0A8Q3SIW6
	MTCL1	NM_001378206.1		c.931C>T	p.Pro311Ser	missense	Exon 1 of 16	NP_001365135.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTCL1	ENST00000695636.1	MANE Select	c.931C>T	p.Pro311Ser	missense	Exon 1 of 15	ENSP00000512073.1	A0A8Q3WKN6
	MTCL1	ENST00000695635.1		c.931C>T	p.Pro311Ser	missense	Exon 1 of 14	ENSP00000512072.1	A0A8Q3SIW6
	MTCL1	ENST00000911533.1		c.931C>T	p.Pro311Ser	missense	Exon 1 of 15	ENSP00000581592.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.2
DANN	Benign	0.82
DEOGEN2	Benign	0.026	T
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.047	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.041
Sift4G	Benign	0.71	T
Vest4		0.038
MVP		0.44
GERP RS		-8.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2
Varity_R		0.019
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1408233142; hg19: chr18-8706589;