rs12602991

Positions:

• chr17-44673150-C-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEIOC	NM_001145080.3	c.2458-216C>A		intron_variant		ENST00000409122.7	NP_001138552.2
MEIOC	XM_005257236.4	c.2458-216C>A		intron_variant			XP_005257293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEIOC	ENST00000409122.7	c.2458-216C>A		intron_variant		5	NM_001145080.3	ENSP00000386452	P1
CCDC43	ENST00000588687.5	c.*308G>T		3_prime_UTR_variant	3/3	2		ENSP00000468079
MEIOC	ENST00000472403.5	c.148-216C>A		intron_variant, NMD_transcript_variant		2		ENSP00000467305

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

Gnomad4 AFR exome AF: 0.0605

Gnomad4 AMR exome AF: 0.0727

Gnomad4 ASJ exome AF: 0.0683

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.0929

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.0930

Gnomad4 OTH exome AF: 0.0885

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

Gnomad4 AFR AF: 0.0661

Gnomad4 AMR AF: 0.0730

Gnomad4 ASJ AF: 0.0678

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.0892

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.0960

Gnomad4 OTH AF: 0.0884

Alfa AF: 0.0901 Hom.: 549

Bravo AF: 0.0817

Asia WGS AF: 0.0970 AC: 336 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.8
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs12602991; hg19: chr17-42750518;