Genetic Variant MAF:p.His185_His187dup (chr16-79599341-C-CGTGGTGGTG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_005360.5(MAF):c.553_561dupCACCACCAC(p.His185_His187dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000324 in 987,398 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

MAF
NM_005360.5 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.08

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_005360.5.

BP6

Variant 16-79599341-C-CGTGGTGGTG is Benign according to our data. Variant chr16-79599341-C-CGTGGTGGTG is described in ClinVar as [Likely_benign]. Clinvar id is 2073859.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5 link	c.553_561dupCACCACCAC	p.His185_His187dup	conservative_inframe_insertion	Exon 1 of 2	ENST00000326043.5	NP_005351.2	O75444-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAF	ENST00000326043.5 link	c.553_561dupCACCACCAC	p.His185_His187dup	conservative_inframe_insertion	Exon 1 of 2	1	NM_005360.5	ENSP00000327048.4	O75444-1
MAF	ENST00000569649.1 link	c.553_561dupCACCACCAC	p.His185_His187dup	conservative_inframe_insertion	Exon 1 of 2	5		ENSP00000455097.1	H3BP11
MAF	ENST00000393350.1 link	c.553_561dupCACCACCAC	p.His185_His187dup	conservative_inframe_insertion	Exon 1 of 1	6		ENSP00000377019.1	O75444-2

Frequencies

GnomAD3 genomes

AF:

0.0000206

AC:

AN:

145492

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000681

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:

0.0000305

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000344

AC:

AN:

841906

Hom.:

Cov.:

AF XY:

0.0000487

AC XY:

AN XY:

390104

show subpopulations

Gnomad4 AFR exome

AF:

0.0000628

Gnomad4 AMR exome

AF:

0.00

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:

0.0000339

Gnomad4 OTH exome

AF:

0.0000718

GnomAD4 genome

AF:

0.0000206

AC:

AN:

145492

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70676

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000681

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000305

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Ayme-Gripp syndrome;C1857768:Cataract 21 multiple types

Benign:1

Dec 18, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

16-79599341-CGTGGTGGTG-CGTGGTGGTGGTGGTGGTG

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