rs2259435

Variant names:

• chr6-31529138-G-A
• rs2259435
• NM_001011700.3:c.124G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31529138-G-A
• chr6-31529138-G-C
• chr6-31529138-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001011700.3(MCCD1):​c.124G>A​(p.Glu42Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,611,260 control chromosomes in the GnomAD database, including 23,750 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.16 (2118 hom., cov: 31)
  • Exomes 𝑓: 0.17 (21632 hom.)
• Consequence: MCCD1 NM_001011700.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 32 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039396584).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCCD1	NM_001011700.3	MANE Select	c.124G>A	p.Glu42Lys	missense	Exon 1 of 2	NP_001011700.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCCD1	ENST00000376191.3	TSL:1 MANE Select	c.124G>A	p.Glu42Lys	missense	Exon 1 of 2	ENSP00000365362.2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24901 AN: 151924 Hom.: 2119 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.184

GnomAD2 exomes AF: 0.179 AC: 43982 AN: 246220 AF XY: 0.186

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.164

Gnomad FIN exome AF: 0.189

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.179

GnomAD4 exome AF: 0.169 AC: 246287 AN: 1459218 Hom.: 21632 Cov.: 67 AF XY: 0.173 AC XY: 125340 AN XY: 725972

African (AFR) AF: 0.145 AC: 4850 AN: 33438

American (AMR) AF: 0.137 AC: 6103 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 5154 AN: 26100

East Asian (EAS) AF: 0.157 AC: 6232 AN: 39694

South Asian (SAS) AF: 0.260 AC: 22380 AN: 86226

European-Finnish (FIN) AF: 0.185 AC: 9663 AN: 52298

Middle Eastern (MID) AF: 0.201 AC: 1161 AN: 5762

European-Non Finnish (NFE) AF: 0.162 AC: 180114 AN: 1110684

Other (OTH) AF: 0.176 AC: 10630 AN: 60320

GnomAD4 genome AF: 0.164 AC: 24918 AN: 152042 Hom.: 2118 Cov.: 31 AF XY: 0.165 AC XY: 12247 AN XY: 74316

African (AFR) AF: 0.143 AC: 5935 AN: 41474

American (AMR) AF: 0.153 AC: 2344 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 675 AN: 3472

East Asian (EAS) AF: 0.163 AC: 840 AN: 5162

South Asian (SAS) AF: 0.261 AC: 1257 AN: 4820

European-Finnish (FIN) AF: 0.179 AC: 1897 AN: 10592

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11459 AN: 67930

Other (OTH) AF: 0.184 AC: 387 AN: 2102

Alfa AF: 0.174 Hom.: 6233

Bravo AF: 0.162

TwinsUK AF: 0.173 AC: 640

ALSPAC AF: 0.156 AC: 600

ESP6500AA AF: 0.146 AC: 442

ESP6500EA AF: 0.171 AC: 926

ExAC AF: 0.181 AC: 21307

Asia WGS AF: 0.237 AC: 824 AN: 3478

EpiCase AF: 0.180

EpiControl AF: 0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.0
DANN	Benign	0.90
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.095	N
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.041
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.011
Sift	Benign	0.098	T
Sift4G	Benign	0.55	T
Polyphen		0.034	B
Vest4		0.032
MPC		0.20
ClinPred		0.00059	T
GERP RS		-0.64
PromoterAI		0.00010	Neutral
Varity_R		0.032
gMVP		0.095
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2259435; hg19: chr6-31496915; COSMIC: COSV66018513; COSMIC: COSV66018513;