chr16-1844911-C-T

Variant names:

• chr16-1844911-C-T
• rs9806826
• NM_001163560.3:c.831G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001163560.3(MEIOB):​c.831G>A​(p.Thr277Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,526,526 control chromosomes in the GnomAD database, including 72,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.33 (8207 hom., cov: 32)
  • Exomes 𝑓: 0.30 (64100 hom.)
• Consequence: MEIOB NM_001163560.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.158
• Publications: 30 publications found

Genes affected

MEIOB (HGNC:28569): (meiosis specific with OB-fold) Predicted to enable chromatin binding activity; single-stranded DNA 3'-5' exodeoxyribonuclease activity; and single-stranded DNA binding activity. Predicted to be involved in double-strand break repair via homologous recombination; fertilization; and meiotic nuclear division. Predicted to be located in cytoplasm. Implicated in spermatogenic failure 22. [provided by Alliance of Genome Resources, Apr 2022]

MEIOB Gene-Disease associations (from GenCC):

• spermatogenic failure 22

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 16-1844911-C-T is Benign according to our data. Variant chr16-1844911-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060040.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.158 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163560.3. 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
	MEIOB	NM_001163560.3	MANE Select	c.831G>A	p.Thr277Thr	synonymous	Exon 10 of 14	NP_001157032.1	Q8N635-2
	MEIOB	NM_152764.3		c.831G>A	p.Thr277Thr	synonymous	Exon 10 of 13	NP_689977.2	Q8N635-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIOB	ENST00000325962.9	TSL:5 MANE Select	c.831G>A	p.Thr277Thr	synonymous	Exon 10 of 14	ENSP00000314484.3	Q8N635-2
	MEIOB	ENST00000397344.7	TSL:5	c.831G>A	p.Thr277Thr	synonymous	Exon 10 of 13	ENSP00000380504.3	Q8N635-1
	MEIOB	ENST00000470044.5	TSL:2	c.210G>A	p.Thr70Thr	synonymous	Exon 9 of 13	ENSP00000457416.1	H3BU10

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49467 AN: 151844 Hom.: 8207 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.302

GnomAD2 exomes AF: 0.322 AC: 77564 AN: 241088 AF XY: 0.327

Gnomad AFR exome AF: 0.332

Gnomad AMR exome AF: 0.247

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.420

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.292

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.296 AC: 407043 AN: 1374564 Hom.: 64100 Cov.: 24 AF XY: 0.301 AC XY: 206483 AN XY: 684890

African (AFR) AF: 0.319 AC: 10039 AN: 31490

American (AMR) AF: 0.259 AC: 11052 AN: 42722

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 6827 AN: 25260

East Asian (EAS) AF: 0.477 AC: 18360 AN: 38476

South Asian (SAS) AF: 0.416 AC: 33458 AN: 80346

European-Finnish (FIN) AF: 0.393 AC: 20623 AN: 52438

Middle Eastern (MID) AF: 0.279 AC: 1544 AN: 5526

European-Non Finnish (NFE) AF: 0.276 AC: 287811 AN: 1041160

Other (OTH) AF: 0.303 AC: 17329 AN: 57146

GnomAD4 genome AF: 0.326 AC: 49494 AN: 151962 Hom.: 8207 Cov.: 32 AF XY: 0.334 AC XY: 24771 AN XY: 74236

African (AFR) AF: 0.335 AC: 13884 AN: 41442

American (AMR) AF: 0.318 AC: 4849 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 938 AN: 3468

East Asian (EAS) AF: 0.436 AC: 2253 AN: 5168

South Asian (SAS) AF: 0.420 AC: 2024 AN: 4820

European-Finnish (FIN) AF: 0.408 AC: 4294 AN: 10518

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20291 AN: 67986

Other (OTH) AF: 0.298 AC: 628 AN: 2104

Alfa AF: 0.298 Hom.: 9542

Bravo AF: 0.313

Asia WGS AF: 0.414 AC: 1438 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.4
DANN	Benign	0.67
PhyloP100		0.16
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: rs9806826; hg19: chr16-1894912; COSMIC: COSV58053219; COSMIC: COSV58053219;