Variant 18-8706488-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001395333.1(MTCL1):c.828G>A(p.Ala276=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 1,269,540 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 35 hom., cov: 33)

Exomes 𝑓: 0.020 ( 271 hom. )

Consequence

MTCL1
NM_001395333.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0320

Variant links:

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 links:

GACAT2 (HGNC:50516): (gastric cancer associated transcript 2)

GACAT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 18-8706488-G-A is Benign according to our data. Variant chr18-8706488-G-A is described in ClinVar as [Benign]. Clinvar id is 3068677.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.032 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0153 (2320/151974) while in subpopulation SAS AF= 0.029 (140/4822). AF 95% confidence interval is 0.0251. There are 35 homozygotes in gnomad4. There are 1166 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTCL1	NM_001395333.1 linkuse as main transcript	c.828G>A	p.Ala276=	synonymous_variant	1/15	ENST00000695636.1
GACAT2	NR_120598.1 linkuse as main transcript	n.552+582C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTCL1	ENST00000695636.1 linkuse as main transcript	c.828G>A	p.Ala276=	synonymous_variant	1/15		NM_001395333.1	A2
GACAT2	ENST00000579368.2 linkuse as main transcript	n.630+582C>T		intron_variant, non_coding_transcript_variant		2
MTCL1	ENST00000695635.1 linkuse as main transcript	c.828G>A	p.Ala276=	synonymous_variant	1/14			A2
MTCL1	ENST00000306329.16 linkuse as main transcript	c.828G>A	p.Ala276=	synonymous_variant	1/15	5		A2	Q9Y4B5-1

Frequencies

GnomAD3 genomes

AF:

0.0153

AC:

2319

AN:

151868

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00386

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.0597

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0282

Gnomad FIN

AF:

0.0142

Gnomad MID

AF:

0.0764

Gnomad NFE

AF:

0.0197

Gnomad OTH

AF:

0.0254

GnomAD3 exomes

AF:

0.0275

AC:

AN:

546

Hom.:

AF XY:

0.0242

AC XY:

AN XY:

330

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0431

Gnomad NFE exome

AF:

0.0234

Gnomad OTH exome

AF:

0.0625

GnomAD4 exome

AF:

0.0198

AC:

22129

AN:

1117566

Hom.:

271

Cov.:

AF XY:

0.0202

AC XY:

10743

AN XY:

531770

show subpopulations

Gnomad4 AFR exome

AF:

0.00318

Gnomad4 AMR exome

AF:

0.0149

Gnomad4 ASJ exome

AF:

0.0545

Gnomad4 EAS exome

AF:

0.0000377

Gnomad4 SAS exome

AF:

0.0349

Gnomad4 FIN exome

AF:

0.0127

Gnomad4 NFE exome

AF:

0.0198

Gnomad4 OTH exome

AF:

0.0221

GnomAD4 genome

AF:

0.0153

AC:

2320

AN:

151974

Hom.:

Cov.:

AF XY:

0.0157

AC XY:

1166

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00385

Gnomad4 AMR

AF:

0.0128

Gnomad4 ASJ

AF:

0.0597

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0290

Gnomad4 FIN

AF:

0.0142

Gnomad4 NFE

AF:

0.0197

Gnomad4 OTH

AF:

0.0247

Alfa

AF:

0.0148

Hom.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.0100

AC:

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cerebellar ataxia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics, Royal Melbourne Hospital

May 04, 2023

European Non-Finnish population allele frequency is 1.223% (rs151052217, 239/15674 alleles, 1 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, this variant is classified as BENIGN. Following criteria are met: BA1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.8

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over