Variant 6-7727238-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 4P and 3B. PS1_ModeratePM1BP4BP6_Moderate

The NM_001718.6(BMP6):c.283C>T(p.Pro95Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000327 in 1,606,518 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in UniProt.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 1 hom. )

Consequence

BMP6
NM_001718.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 5.34

Variant links:

Genes affected

BMP6 (HGNC:1073): (bone morphogenetic protein 6) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates a wide range of biological processes including iron homeostasis, fat and bone development, and ovulation. Differential expression of this gene may be associated with progression of breast and prostate cancer. Mutations in this gene may be associated with iron overload in human patients. [provided by RefSeq, Jul 2016]

BMP6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PS1

Transcript NM_001718.6 (BMP6) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt

PM1

In a region_of_interest Disordered (size 42) in uniprot entity BMP6_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_001718.6

BP4

Computational evidence support a benign effect (MetaRNN=0.40516105).

BP6

Variant 6-7727238-C-T is Benign according to our data. Variant chr6-7727238-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1801214.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP6	NM_001718.6 link	c.283C>T	p.Pro95Ser	missense_variant	1/7	ENST00000283147.7	NP_001709.1	P22004Q4VBA3B4DUF7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP6	ENST00000283147.7 link	c.283C>T	p.Pro95Ser	missense_variant	1/7	1	NM_001718.6	ENSP00000283147.6		P22004

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000242

AC:

AN:

223056

Hom.:

AF XY:

0.000275

AC XY:

AN XY:

123772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000902

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000909

Gnomad FIN exome

AF:

0.000155

Gnomad NFE exome

AF:

0.000207

Gnomad OTH exome

AF:

0.000183

GnomAD4 exome

AF:

0.000343

AC:

499

AN:

1454206

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

255

AN XY:

723016

show subpopulations

Gnomad4 AFR exome

AF:

0.0000900

Gnomad4 AMR exome

AF:

0.000362

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000665

Gnomad4 FIN exome

AF:

0.0000591

Gnomad4 NFE exome

AF:

0.000363

Gnomad4 OTH exome

AF:

0.000200

GnomAD4 genome

AF:

0.000177

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000871

AC:

ExAC

AF:

0.000306

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

BMP6: BS2 -

Iron overload, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Nov 28, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.81

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.74

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.54

MutationAssessor

Benign

2.0

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.37

Sift

Benign

0.054

Sift4G

Uncertain

0.037

Polyphen

1.0

Vest4

0.83

MVP

0.73

MPC

0.57

ClinPred

0.26

GERP RS

1.5

Varity_R

0.21

gMVP

0.57

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