4-139266961-C-G

Variant names:

• chr4-139266961-C-G
• rs367919742
• NM_032623.4:c.361G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032623.4(MGARP):​c.361G>C​(p.Asp121His) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D121N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MGARP NM_032623.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.980
• Publications: 1 publications found

Genes affected

MGARP (HGNC:29969): (mitochondria localized glutamic acid rich protein) Predicted to be involved in several processes, including axonal transport; cellular response to hormone stimulus; and protein targeting to mitochondrion. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

NDUFC1 (HGNC:7705): (NADH:ubiquinone oxidoreductase subunit C1) The encoded protein is a subunit of the NADH:ubiquinone oxidoreductase (complex I), the first enzyme complex in the electron transport chain located in the inner mitochondrial membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ENSG00000288785 (HGNC:58885):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09391883).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032623.4. 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
	MGARP	NM_032623.4	MANE Select	c.361G>C	p.Asp121His	missense	Exon 4 of 4	NP_116012.2	Q8TDB4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGARP	ENST00000398955.2	TSL:1 MANE Select	c.361G>C	p.Asp121His	missense	Exon 4 of 4	ENSP00000381928.1	Q8TDB4
	MGARP	ENST00000962439.1		c.281-61G>C		intron	N/A	ENSP00000632498.1
	NDUFC1	ENST00000503997.5	TSL:3	n.*299G>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000425882.1	O43677

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.98
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.050
Sift	Benign	0.54	T
Sift4G	Benign	0.095	T
Polyphen		0.92	P
Vest4		0.087
MutPred		0.26		Gain of sheet (P = 0.0477)
MVP		0.048
MPC		0.50
ClinPred		0.39	T
GERP RS		2.2
Varity_R		0.047
gMVP		0.069
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs367919742; hg19: chr4-140188115;