8-144106852-C-G

Variant names:

• chr8-144106852-C-G
• NM_032272.5:c.638C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032272.5(MAF1):​c.638C>G​(p.Pro213Arg) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAF1 NM_032272.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05067414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF1	NM_032272.5	c.638C>G	p.Pro213Arg	missense_variant	Exon 7 of 8	ENST00000322428.10	NP_115648.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAF1	ENST00000322428.10	c.638C>G	p.Pro213Arg	missense_variant	Exon 7 of 8	1	NM_032272.5	ENSP00000318604.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.045	T;T;T;T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.69	.;T;T;T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.051	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;N;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.18	N;N;N;N;N
REVEL	Benign	0.044
Sift	Benign	0.23	T;T;T;T;T
Sift4G	Benign	0.54	T;T;T;T;D
Polyphen		0.0	B;.;B;.;.
Vest4		0.062
MutPred		0.24		Loss of glycosylation at T210 (P = 0.0215);.;Loss of glycosylation at T210 (P = 0.0215);.;.;
MVP		0.15
MPC		0.0054
ClinPred		0.058	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145161755;