chr18-8706591-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001395333.1(MTCL1):​c.931C>G​(p.Pro311Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,507,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: MTCL1 NM_001395333.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04779643).

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>G	p.Pro311Ala	missense	Exon 1 of 15	NP_001382262.1	A0A8Q3WKN6
	MTCL1	NM_001378207.1		c.931C>G	p.Pro311Ala	missense	Exon 1 of 14	NP_001365136.1	A0A8Q3SIW6
	MTCL1	NM_001378206.1		c.931C>G	p.Pro311Ala	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>G	p.Pro311Ala	missense	Exon 1 of 15	ENSP00000512073.1	A0A8Q3WKN6
	MTCL1	ENST00000695635.1		c.931C>G	p.Pro311Ala	missense	Exon 1 of 14	ENSP00000512072.1	A0A8Q3SIW6
	MTCL1	ENST00000911533.1		c.931C>G	p.Pro311Ala	missense	Exon 1 of 15	ENSP00000581592.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152156 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00000950 AC: 1 AN: 105262 AF XY: 0.0000172

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000332

GnomAD4 exome AF: 0.0000184 AC: 25 AN: 1355152 Hom.: 0 Cov.: 36 AF XY: 0.0000240 AC XY: 16 AN XY: 667156

African (AFR) AF: 0.000565 AC: 16 AN: 28318

American (AMR) AF: 0.00 AC: 0 AN: 30664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23674

East Asian (EAS) AF: 0.00 AC: 0 AN: 31980

South Asian (SAS) AF: 0.00 AC: 0 AN: 74638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44412

Middle Eastern (MID) AF: 0.000241 AC: 1 AN: 4156

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1061328

Other (OTH) AF: 0.000143 AC: 8 AN: 55982

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152156 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74328

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.7
DANN	Benign	0.51
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.048	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.041
Sift4G	Benign	0.86	T
Vest4		0.071
MVP		0.44
GERP RS		-8.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2
Varity_R		0.018
Mutation Taster		=97/3	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;