18-8705999-G-A

Position:

• chr18-8705999-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001395333.1(MTCL1):​c.339G>A​(p.Pro113Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,152,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: MTCL1 NM_001395333.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0130

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]

MTCL1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-8705999-G-A is Benign according to our data. Variant chr18-8705999-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3388279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.013 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTCL1	NM_001395333.1	c.339G>A	p.Pro113Pro	synonymous_variant	1/15	ENST00000695636.1	NP_001382262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTCL1	ENST00000695636.1	c.339G>A	p.Pro113Pro	synonymous_variant	1/15		NM_001395333.1	ENSP00000512073.1
MTCL1	ENST00000695635.1	c.339G>A	p.Pro113Pro	synonymous_variant	1/14			ENSP00000512072.1
MTCL1	ENST00000306329.16	c.339G>A	p.Pro113Pro	synonymous_variant	1/15	5		ENSP00000305027.11
GACAT2	ENST00000579368.2	n.630+1071C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.000188 AC: 28 AN: 148754 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000334

Gnomad ASJ AF: 0.00117

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00189

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000900

Gnomad OTH AF: 0.00146

GnomAD4 exome AF: 0.000107 AC: 107 AN: 1003700 Hom.: 0 Cov.: 34 AF XY: 0.000112 AC XY: 53 AN XY: 472430

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000678

Gnomad4 ASJ exome AF: 0.00226

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000531

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000596

Gnomad4 OTH exome AF: 0.000316

GnomAD4 genome AF: 0.000188 AC: 28 AN: 148860 Hom.: 0 Cov.: 32 AF XY: 0.000248 AC XY: 18 AN XY: 72602

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.000333

Gnomad4 ASJ AF: 0.00117

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00189

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000900

Gnomad4 OTH AF: 0.00145

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000166

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

MTCL1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs948015725; hg19: chr18-8705997;