18-8784116-A-G

Variant names:

• chr18-8784116-A-G
• rs1437228101
• NM_001395333.1:c.2084A>G

Variant summary

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

The NM_001395333.1(MTCL1):​c.2084A>G​(p.Gln695Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. Q695P) 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: 6.97
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTCL1	NM_001395333.1	c.2084A>G	p.Gln695Arg	missense_variant	Exon 5 of 15	ENST00000695636.1	NP_001382262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTCL1	ENST00000695636.1	c.2084A>G	p.Gln695Arg	missense_variant	Exon 5 of 15		NM_001395333.1	ENSP00000512073.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 91

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Benign	0.91
DEOGEN2	Benign	0.25	T;.;.;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.81	T;D;.;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.46	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.7	M;.;.;.
PhyloP100		7.0
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.3	.;D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0010	.;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.95	.;.;P;P
Vest4		0.74
MutPred		0.11		.;Gain of methylation at Q335 (P = 0.0371);Gain of methylation at Q335 (P = 0.0371);Gain of methylation at Q335 (P = 0.0371);
MVP		0.44
MPC		0.45
ClinPred		0.93	D
GERP RS		5.6
Varity_R		0.14
gMVP		0.36

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: rs1437228101; hg19: chr18-8784114;