chr6-31529087-C-A

Variant names:

• chr6-31529087-C-A
• NM_001011700.3:c.73C>A

Variant summary

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

The NM_001011700.3(MCCD1):​c.73C>A​(p.Pro25Thr) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MCCD1 NM_001011700.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.175
• Publications: 0 publications found

Genes affected

MCCD1 (HGNC:20668): (mitochondrial coiled-coil domain 1) Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08184984).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011700.3. 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
	MCCD1	NM_001011700.3	MANE Select	c.73C>A	p.Pro25Thr	missense	Exon 1 of 2	NP_001011700.2	P59942

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCCD1	ENST00000376191.3	TSL:1 MANE Select	c.73C>A	p.Pro25Thr	missense	Exon 1 of 2	ENSP00000365362.2	P59942

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.4
DANN	Benign	0.86
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.089	N
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.17
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.063
Sift	Benign	0.051	T
Sift4G	Benign	0.071	T
Polyphen		0.56	P
Vest4		0.17
MutPred		0.23		Loss of disorder (P = 0.0716)
MVP		0.014
MPC		0.20
ClinPred		0.11	T
GERP RS		0.70
PromoterAI		-0.060	Neutral
Varity_R		0.042
gMVP		0.10
Mutation Taster		=99/1	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

hg19: chr6-31496864;