rs8084760

chr18-8792046-A-G

Variant summary

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

The NM_001395333.1(MTCL1):c.2968-952A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,132 control chromosomes in the GnomAD database, including 2,625 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 0.18 (2625 hom., cov: 33)
• Consequence: MTCL1 NM_001395333.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTCL1	NM_001395333.1	c.2968-952A>G		intron_variant		ENST00000695636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTCL1	ENST00000695636.1	c.2968-952A>G		intron_variant			NM_001395333.1	A2

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26831 AN: 152014 Hom.: 2623 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.0970

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.176 AC: 26845 AN: 152132 Hom.: 2625 Cov.: 33 AF XY: 0.179 AC XY: 13298 AN XY: 74386

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0967

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.173

Alfa AF: 0.158 Hom.: 4277

Bravo AF: 0.168

Asia WGS AF: 0.310 AC: 1074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.067
Dann	Benign	0.21

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: rs8084760; hg19: chr18-8792044;