NM_005360.5:c.-12_-7delGGCGGC

Variant names:

• chr16-79599908-TGCCGCC-T
• rs5818251
• NM_005360.5:c.-12_-7delGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_005360.5(MAF):​c.-12_-7delGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 1,466,666 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: MAF NM_005360.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.63
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• Ayme-Gripp syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• cataract 21 multiple types

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics
• cataract - microcornea syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cerulean cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pulverulent cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Fine-Lubinsky syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000278058 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 16-79599908-TGCCGCC-T is Benign according to our data. Variant chr16-79599908-TGCCGCC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2646891.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005360.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAF	NM_005360.5	MANE Select	c.-12_-7delGGCGGC		5_prime_UTR	Exon 1 of 2	NP_005351.2
	MAF	NM_001031804.3		c.-12_-7delGGCGGC		5_prime_UTR	Exon 1 of 1	NP_001026974.1	O75444-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAF	ENST00000326043.5	TSL:1 MANE Select	c.-12_-7delGGCGGC		5_prime_UTR	Exon 1 of 2	ENSP00000327048.4	O75444-1
	MAF	ENST00000393350.1	TSL:6	c.-12_-7delGGCGGC		5_prime_UTR	Exon 1 of 1	ENSP00000377019.1	O75444-2
	ENSG00000278058	ENST00000767269.1		n.44_49delCGCCGC		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.000173 AC: 26 AN: 150622 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000857

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000163

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00135 AC: 265 AN: 195638 AF XY: 0.00128

Gnomad AFR exome AF: 0.00230

Gnomad AMR exome AF: 0.00289

Gnomad ASJ exome AF: 0.000455

Gnomad EAS exome AF: 0.00142

Gnomad FIN exome AF: 0.00158

Gnomad NFE exome AF: 0.000889

Gnomad OTH exome AF: 0.00121

GnomAD4 exome AF: 0.000354 AC: 466 AN: 1315942 Hom.: 0 AF XY: 0.000369 AC XY: 242 AN XY: 656058

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000268 AC: 8 AN: 29846

American (AMR) AF: 0.00222 AC: 89 AN: 40002

Ashkenazi Jewish (ASJ) AF: 0.000210 AC: 5 AN: 23760

East Asian (EAS) AF: 0.000639 AC: 21 AN: 32852

South Asian (SAS) AF: 0.000450 AC: 36 AN: 80038

European-Finnish (FIN) AF: 0.000889 AC: 30 AN: 33754

Middle Eastern (MID) AF: 0.000467 AC: 2 AN: 4282

European-Non Finnish (NFE) AF: 0.000258 AC: 262 AN: 1017038

Other (OTH) AF: 0.000239 AC: 13 AN: 54370

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000173 AC: 26 AN: 150724 Hom.: 0 Cov.: 0 AF XY: 0.000163 AC XY: 12 AN XY: 73622

African (AFR) AF: 0.0000243 AC: 1 AN: 41156

American (AMR) AF: 0.000856 AC: 13 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 4966

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000163 AC: 11 AN: 67500

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0226 Hom.: 4066

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=290/10	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5818251; hg19: chr16-79633805;