22-41699640-C-T

Variant names:

• chr22-41699640-C-T
• rs200066340
• NM_152513.4:c.102C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_152513.4(MEI1):​c.102C>T​(p.Arg34Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000914 in 1,602,354 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0011 (3 hom., cov: 34)
  • Exomes 𝑓: 0.00090 (10 hom.)
• Consequence: MEI1 NM_152513.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.71
• Publications: 2 publications found

Genes affected

MEI1 (HGNC:28613): (meiotic double-stranded break formation protein 1) Predicted to be involved in meiosis I. Predicted to act upstream of or within gamete generation; meiotic spindle organization; and meiotic telomere clustering. Implicated in gestational trophoblastic neoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MEI1 Gene-Disease associations (from GenCC):

• hydatidiform mole, recurrent, 3

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• complete hydatidiform mole

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 22-41699640-C-T is Benign according to our data. Variant chr22-41699640-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3041258.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.71 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00109 (166/152378) while in subpopulation EAS AF = 0.0218 (113/5184). AF 95% confidence interval is 0.0185. There are 3 homozygotes in GnomAd4. There are 89 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152513.4. 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
	MEI1	NM_152513.4	MANE Select	c.102C>T	p.Arg34Arg	synonymous	Exon 1 of 31	NP_689726.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEI1	ENST00000401548.8	TSL:1 MANE Select	c.102C>T	p.Arg34Arg	synonymous	Exon 1 of 31	ENSP00000384115.3	Q5TIA1-1
	MEI1	ENST00000540833.1	TSL:5	c.-679C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	ENSP00000444225.1	F5GZT0
	MEI1	ENST00000890163.1		c.102C>T	p.Arg34Arg	synonymous	Exon 1 of 30	ENSP00000560222.1

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 165 AN: 152262 Hom.: 3 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00185 AC: 403 AN: 218298 AF XY: 0.00179

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000124

Gnomad ASJ exome AF: 0.000645

Gnomad EAS exome AF: 0.0170

Gnomad FIN exome AF: 0.00228

Gnomad NFE exome AF: 0.000265

Gnomad OTH exome AF: 0.00110

GnomAD4 exome AF: 0.000895 AC: 1298 AN: 1449976 Hom.: 10 Cov.: 31 AF XY: 0.000913 AC XY: 658 AN XY: 720464

African (AFR) AF: 0.00 AC: 0 AN: 33352

American (AMR) AF: 0.0000694 AC: 3 AN: 43224

Ashkenazi Jewish (ASJ) AF: 0.000503 AC: 13 AN: 25844

East Asian (EAS) AF: 0.0231 AC: 907 AN: 39228

South Asian (SAS) AF: 0.00111 AC: 94 AN: 84960

European-Finnish (FIN) AF: 0.00210 AC: 107 AN: 51056

Middle Eastern (MID) AF: 0.00159 AC: 9 AN: 5646

European-Non Finnish (NFE) AF: 0.0000994 AC: 110 AN: 1106848

Other (OTH) AF: 0.000919 AC: 55 AN: 59818

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152378 Hom.: 3 Cov.: 34 AF XY: 0.00119 AC XY: 89 AN XY: 74514

African (AFR) AF: 0.00 AC: 0 AN: 41590

American (AMR) AF: 0.000196 AC: 3 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.0218 AC: 113 AN: 5184

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4832

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68042

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000284 Hom.: 0

Bravo AF: 0.000820

Asia WGS AF: 0.00867 AC: 30 AN: 3474

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MEI1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		1.7
PromoterAI		-0.14	Neutral
Mutation Taster		=267/33	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: rs200066340; hg19: chr22-42095644;