rs867401075

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005360.5(MAF):c.611G>T(p.Gly204Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 979,642 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 28 hom., cov: 30)

Exomes 𝑓: 0.00077 ( 7 hom. )

Consequence

MAF
NM_005360.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.223

Variant links:

Genes affected

MAF (HGNC:6776): (MAF bZIP transcription factor) The protein encoded by this gene is a DNA-binding, leucine zipper-containing transcription factor that acts as a homodimer or as a heterodimer. Depending on the binding site and binding partner, the encoded protein can be a transcriptional activator or repressor. This protein plays a role in the regulation of several cellular processes, including embryonic lens fiber cell development, increased T-cell susceptibility to apoptosis, and chondrocyte terminal differentiation. Defects in this gene are a cause of juvenile-onset pulverulent cataract as well as congenital cerulean cataract 4 (CCA4). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

MAF links:

MAF (HGNC:):

MAF 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 (MetaRNN=0.0066075623).

BP6

Variant 16-79599292-C-A is Benign according to our data. Variant chr16-79599292-C-A is described in ClinVar as [Benign]. Clinvar id is 474936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1550/145386) while in subpopulation AFR AF= 0.0354 (1442/40698). AF 95% confidence interval is 0.0339. There are 28 homozygotes in gnomad4. There are 716 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1550 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAF	NM_005360.5 linkuse as main transcript	c.611G>T	p.Gly204Val	missense_variant	1/2	ENST00000326043.5	NP_005351.2	O75444-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAF	ENST00000326043.5 linkuse as main transcript	c.611G>T	p.Gly204Val	missense_variant	1/2	1	NM_005360.5	ENSP00000327048.4	O75444-1
MAF	ENST00000569649.1 linkuse as main transcript	c.611G>T	p.Gly204Val	missense_variant	1/2	5		ENSP00000455097.1	H3BP11
MAF	ENST00000393350.1 linkuse as main transcript	c.611G>T	p.Gly204Val	missense_variant	1/1	6		ENSP00000377019.1	O75444-2

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1548

AN:

145380

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0354

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00483

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000229

Gnomad OTH

AF:

0.0109

GnomAD4 exome

AF:

0.000771

AC:

643

AN:

834256

Hom.:

Cov.:

AF XY:

0.000737

AC XY:

284

AN XY:

385358

show subpopulations

Gnomad4 AFR exome

AF:

0.0323

Gnomad4 AMR exome

AF:

0.00294

Gnomad4 ASJ exome

AF:

0.000967

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000590

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000110

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.0107

AC:

1550

AN:

145386

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

716

AN XY:

70638

show subpopulations

Gnomad4 AFR

AF:

0.0354

Gnomad4 AMR

AF:

0.00483

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000229

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00202

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Ayme-Gripp syndrome;C1857768:Cataract 21 multiple types

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 16, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2022

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.17

.;.;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.57

T;T;T

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.0066

T;T;T

MetaSVM

Uncertain

-0.10

MutationAssessor

Benign

0.34

.;N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.090

N;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.023

D;D;D

Sift4G

Benign

0.41

T;T;T

Polyphen

0.10, 0.015

.;B;B

Vest4

0.20

MutPred

0.17

Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);

MVP

0.72

ClinPred

0.071

GERP RS

0.96

Varity_R

0.16

gMVP

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