rs12602991

Variant names:

• chr17-44673150-C-A
• rs12602991
• NM_001145080.3:c.2458-216C>A

Variant summary

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

The NM_001145080.3(MEIOC):​c.2458-216C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 415,712 control chromosomes in the GnomAD database, including 1,932 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.087 (633 hom., cov: 32)
  • Exomes 𝑓: 0.094 (1299 hom.)
• Consequence: MEIOC NM_001145080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701
• Publications: 1 publications found

Genes affected

MEIOC (HGNC:26670): (meiosis specific with coiled-coil domain) Predicted to be involved in several processes, including gamete generation; germline cell cycle switching, mitotic to meiotic cell cycle; and mRNA stabilization. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CCDC43 (HGNC:26472): (coiled-coil domain containing 43) Located in cytosol. [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 (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145080.3. 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
	MEIOC	NM_001145080.3	MANE Select	c.2458-216C>A		intron	N/A	NP_001138552.2	A2RUB1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIOC	ENST00000409122.7	TSL:5 MANE Select	c.2458-216C>A		intron	N/A	ENSP00000386452.1	A2RUB1-4
	CCDC43	ENST00000588687.5	TSL:2	c.*308G>T		3_prime_UTR	Exon 3 of 3	ENSP00000468079.1	K7ER24
	MEIOC	ENST00000856682.1		c.2353-216C>A		intron	N/A	ENSP00000526741.1

Frequencies

GnomAD3 genomes AF: 0.0872 AC: 13258 AN: 152078 Hom.: 631 Cov.: 32

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.0678

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0889

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.0879

GnomAD4 exome AF: 0.0937 AC: 24683 AN: 263514 Hom.: 1299 Cov.: 2 AF XY: 0.0949 AC XY: 12770 AN XY: 134608

African (AFR) AF: 0.0605 AC: 434 AN: 7168

American (AMR) AF: 0.0727 AC: 632 AN: 8698

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 642 AN: 9400

East Asian (EAS) AF: 0.123 AC: 2774 AN: 22494

South Asian (SAS) AF: 0.0929 AC: 715 AN: 7694

European-Finnish (FIN) AF: 0.104 AC: 2231 AN: 21386

Middle Eastern (MID) AF: 0.0694 AC: 93 AN: 1340

European-Non Finnish (NFE) AF: 0.0930 AC: 15637 AN: 168100

Other (OTH) AF: 0.0885 AC: 1525 AN: 17234

GnomAD4 genome AF: 0.0872 AC: 13266 AN: 152198 Hom.: 633 Cov.: 32 AF XY: 0.0880 AC XY: 6545 AN XY: 74412

African (AFR) AF: 0.0661 AC: 2744 AN: 41528

American (AMR) AF: 0.0730 AC: 1117 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0678 AC: 235 AN: 3468

East Asian (EAS) AF: 0.143 AC: 743 AN: 5184

South Asian (SAS) AF: 0.0892 AC: 430 AN: 4822

European-Finnish (FIN) AF: 0.117 AC: 1238 AN: 10580

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0960 AC: 6531 AN: 68002

Other (OTH) AF: 0.0884 AC: 187 AN: 2116

Alfa AF: 0.0882 Hom.: 677

Bravo AF: 0.0817

Asia WGS AF: 0.0970 AC: 336 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.8
DANN	Benign	0.73
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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: rs12602991; hg19: chr17-42750518;