rs4798680

chr18-8730728-G-Achr18-8730728-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395333.1(MTCL1):c.1437+10232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,038 control chromosomes in the GnomAD database, including 9,093 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (9093 hom., cov: 32)
• Consequence: MTCL1 NM_001395333.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTCL1	NM_001395333.1	c.1437+10232G>A		intron_variant		ENST00000695636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTCL1	ENST00000695636.1	c.1437+10232G>A		intron_variant			NM_001395333.1	A2

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49703 AN: 151920 Hom.: 9087 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.351

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.327 AC: 49716 AN: 152038 Hom.: 9093 Cov.: 32 AF XY: 0.329 AC XY: 24453 AN XY: 74322

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.357

Alfa AF: 0.332 Hom.: 1316

Bravo AF: 0.314

Asia WGS AF: 0.494 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.2
Dann	Benign	0.65

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: rs4798680; hg19: chr18-8730726;