16-79599188-C-T

Position:

chr16-79599188-C-T

Variant summary

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

The NM_005360.5(MAF):c.715G>A(p.Ala239Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000767 in 1,058,356 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 16 hom., cov: 29)

Exomes 𝑓: 0.00040 ( 19 hom. )

Consequence

MAF
NM_005360.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.129

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=0.0010850132).

BP6

Variant 16-79599188-C-T is Benign according to our data. Variant chr16-79599188-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 474938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-79599188-C-T is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAF	NM_005360.5 linkuse as main transcript	c.715G>A	p.Ala239Thr	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.715G>A	p.Ala239Thr	missense_variant	1/2	1	NM_005360.5	ENSP00000327048.4	O75444-1
MAF	ENST00000569649.1 linkuse as main transcript	c.715G>A	p.Ala239Thr	missense_variant	1/2	5		ENSP00000455097.1	H3BP11
MAF	ENST00000393350.1 linkuse as main transcript	c.715G>A	p.Ala239Thr	missense_variant	1/1	6		ENSP00000377019.1	O75444-2

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

445

AN:

145852

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000467

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0284

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:

0.0000152

Gnomad OTH

AF:

0.00399

GnomAD3 exomes

AF:

0.0827

AC:

AN:

532

Hom.:

AF XY:

0.0645

AC XY:

AN XY:

310

show subpopulations

Gnomad AMR exome

AF:

0.477

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.000402

AC:

367

AN:

912466

Hom.:

Cov.:

AF XY:

0.000366

AC XY:

156

AN XY:

426558

show subpopulations

Gnomad4 AFR exome

AF:

0.000112

Gnomad4 AMR exome

AF:

0.0871

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000618

Gnomad4 OTH exome

AF:

0.00120

GnomAD4 genome

AF:

0.00305

AC:

445

AN:

145890

Hom.:

Cov.:

AF XY:

0.00346

AC XY:

245

AN XY:

70892

show subpopulations

Gnomad4 AFR

AF:

0.000466

Gnomad4 AMR

AF:

0.0284

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000152

Gnomad4 OTH

AF:

0.00396

Bravo

AF:

0.00462

ExAC

AF:

0.00471

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 30, 2020	- -

Ayme-Gripp syndrome;C1857768:Cataract 21 multiple types

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.19

.;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.41

T;T;T

MetaRNN

Benign

0.0011

T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.0

.;N;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.41

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.67

T;T;T

Sift4G

Benign

0.41

T;T;T

Polyphen

0.0, 0.0060

.;B;B

Vest4

0.13

MutPred

0.26

Gain of glycosylation at A239 (P = 0.0039);Gain of glycosylation at A239 (P = 0.0039);Gain of glycosylation at A239 (P = 0.0039);

ClinPred

0.029

GERP RS

-4.3

Varity_R

0.046

gMVP

0.20

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