8-144106203-C-G

Position:

• chr8-144106203-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032272.5(MAF1):​c.340C>G​(p.Arg114Gly) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAF1 NM_032272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3676014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAF1	NM_032272.5	c.340C>G	p.Arg114Gly	missense_variant	4/8	ENST00000322428.10	NP_115648.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAF1	ENST00000322428.10	c.340C>G	p.Arg114Gly	missense_variant	4/8	1	NM_032272.5	ENSP00000318604	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.340C>G (p.R114G) alteration is located in exon 4 (coding exon 3) of the MAF1 gene. This alteration results from a C to G substitution at nucleotide position 340, causing the arginine (R) at amino acid position 114 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	0.0085	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;T;T;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.074
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.96	.;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M;.;M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.5	D;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.88	P;.;P;.
Vest4		0.46
MutPred		0.49		Loss of methylation at R114 (P = 0.0357);Loss of methylation at R114 (P = 0.0357);Loss of methylation at R114 (P = 0.0357);Loss of methylation at R114 (P = 0.0357);
MVP		0.47
MPC		2.0
ClinPred		0.98	D
GERP RS		1.9
Varity_R		0.68
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145161106;