Variant 14-75022929-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001040108.2(MLH3):c.4012-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 1,613,404 control chromosomes in the GnomAD database, including 175,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16571 hom., cov: 31)

Exomes 𝑓: 0.46 ( 159269 hom. )

Consequence

MLH3
NM_001040108.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0790

Variant links:

Genes affected

MLH3 (HGNC:7128): (mutL homolog 3) This gene is a member of the MutL-homolog (MLH) family of DNA mismatch repair (MMR) genes. MLH genes are implicated in maintaining genomic integrity during DNA replication and after meiotic recombination. The protein encoded by this gene functions as a heterodimer with other family members. Somatic mutations in this gene frequently occur in tumors exhibiting microsatellite instability, and germline mutations have been linked to hereditary nonpolyposis colorectal cancer type 7 (HNPCC7). Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Jul 2008]

MLH3 links:

MLH3 (HGNC:):

MLH3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 14-75022929-C-T is Benign according to our data. Variant chr14-75022929-C-T is described in ClinVar as [Benign]. Clinvar id is 1242252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLH3	NM_001040108.2 linkuse as main transcript	c.4012-37G>A		intron_variant		ENST00000355774.7	NP_001035197.1	Q9UHC1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLH3	ENST00000355774.7 linkuse as main transcript	c.4012-37G>A		intron_variant		5	NM_001040108.2	ENSP00000348020.2		Q9UHC1-1

Frequencies

GnomAD3 genomes

AF:

0.460

AC:

69841

AN:

151872

Hom.:

16551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.509

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.368

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.545

Gnomad NFE

AF:

0.470

Gnomad OTH

AF:

0.464

GnomAD3 exomes

AF:

0.422

AC:

106019

AN:

251460

Hom.:

24092

AF XY:

0.433

AC XY:

58895

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.509

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.488

Gnomad EAS exome

AF:

0.167

Gnomad SAS exome

AF:

0.502

Gnomad FIN exome

AF:

0.456

Gnomad NFE exome

AF:

0.468

Gnomad OTH exome

AF:

0.449

GnomAD4 exome

AF:

0.461

AC:

674408

AN:

1461412

Hom.:

159269

Cov.:

AF XY:

0.463

AC XY:

336952

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.515

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.492

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.501

Gnomad4 FIN exome

AF:

0.458

Gnomad4 NFE exome

AF:

0.474

Gnomad4 OTH exome

AF:

0.461

GnomAD4 genome

AF:

0.460

AC:

69902

AN:

151992

Hom.:

16571

Cov.:

AF XY:

0.457

AC XY:

33955

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.508

Gnomad4 AMR

AF:

0.368

Gnomad4 ASJ

AF:

0.493

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.506

Gnomad4 FIN

AF:

0.446

Gnomad4 NFE

AF:

0.470

Gnomad4 OTH

AF:

0.471

Alfa

AF:

0.465

Hom.:

9353

Bravo

AF:

0.451

Asia WGS

AF:

0.394

AC:

1371

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.7

DANN

Benign

0.46

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

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