8-144105743-T-G

Variant names:

• chr8-144105743-T-G
• NM_032272.5:c.60T>G
• MAF1 p.Thr20Thr

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_032272.5(MAF1):​c.60T>G​(p.Thr20Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T20T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MAF1 NM_032272.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.91
• Publications: 0 publications found

Genes affected

MAF1 (HGNC:24966): (MAF1 homolog, negative regulator of RNA polymerase III) This gene encodes a protein that is similar to Maf1, a Saccharomyces cerevisiae protein highly conserved in eukaryotic cells. Yeast Maf1 is a negative effector of RNA polymerase III (Pol III). It responds to changes in the cellular environment and represses pol III transcription. Biochemical studies identified the initiation factor TFIIIB as a target for Maf1-dependent repression. [provided by RefSeq, Jul 2008]

SHARPIN (HGNC:25321): (SHANK associated RH domain interactor) Enables polyubiquitin modification-dependent protein binding activity. Involved in protein linear polyubiquitination and regulation of signal transduction. Located in cytosol. Part of LUBAC complex. [provided by Alliance of Genome Resources, Apr 2022]

SHARPIN Gene-Disease associations (from GenCC):

• autoinflammation with episodic fever and immune dysregulation

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-3.91 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032272.5. 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
	MAF1	NM_032272.5	MANE Select	c.60T>G	p.Thr20Thr	synonymous	Exon 2 of 8	NP_115648.2	Q9H063

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAF1	ENST00000322428.10	TSL:1 MANE Select	c.60T>G	p.Thr20Thr	synonymous	Exon 2 of 8	ENSP00000318604.5	Q9H063
	MAF1	ENST00000876672.1		c.60T>G	p.Thr20Thr	synonymous	Exon 2 of 7	ENSP00000546731.1
	MAF1	ENST00000534585.5	TSL:5	c.60T>G	p.Thr20Thr	synonymous	Exon 2 of 7	ENSP00000433979.1	E9PSH4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.029
DANN	Benign	0.44
PhyloP100		-3.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-145160646;