rs75546096

Variant names:

• chr16-1841902-C-A
• rs75546096
• NM_001163560.3:c.952G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-1841902-C-A
• chr16-1841902-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001163560.3(MEIOB):​c.952G>T​(p.Asp318Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000741 in 1,607,680 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (7 hom., cov: 31)
  • Exomes 𝑓: 0.00040 (8 hom.)
• Consequence: MEIOB NM_001163560.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.68
• Publications: 0 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

ENSG00000260541 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009603798).
• BP6: Variant 16-1841902-C-A is Benign according to our data. Variant chr16-1841902-C-A is described in ClinVar as Benign. ClinVar VariationId is 711956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00396 (604/152342) while in subpopulation AFR AF = 0.0139 (578/41580). AF 95% confidence interval is 0.013. There are 7 homozygotes in GnomAd4. There are 318 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR,AD gene

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.952G>T	p.Asp318Tyr	missense	Exon 11 of 14	NP_001157032.1	Q8N635-2
	MEIOB	NM_152764.3		c.952G>T	p.Asp318Tyr	missense	Exon 11 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.952G>T	p.Asp318Tyr	missense	Exon 11 of 14	ENSP00000314484.3	Q8N635-2
	MEIOB	ENST00000397344.7	TSL:5	c.952G>T	p.Asp318Tyr	missense	Exon 11 of 13	ENSP00000380504.3	Q8N635-1
	MEIOB	ENST00000470044.5	TSL:2	c.331G>T	p.Asp111Tyr	missense	Exon 10 of 13	ENSP00000457416.1	H3BU10

Frequencies

GnomAD3 genomes AF: 0.00397 AC: 604 AN: 152224 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00102 AC: 254 AN: 248674 AF XY: 0.000841

Gnomad AFR exome AF: 0.0141

Gnomad AMR exome AF: 0.000508

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000442

Gnomad OTH exome AF: 0.000661

GnomAD4 exome AF: 0.000403 AC: 587 AN: 1455338 Hom.: 8 Cov.: 29 AF XY: 0.000347 AC XY: 251 AN XY: 723862

African (AFR) AF: 0.0145 AC: 482 AN: 33350

American (AMR) AF: 0.000951 AC: 42 AN: 44184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5702

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1108258

Other (OTH) AF: 0.000765 AC: 46 AN: 60156

GnomAD4 genome AF: 0.00396 AC: 604 AN: 152342 Hom.: 7 Cov.: 31 AF XY: 0.00427 AC XY: 318 AN XY: 74496

African (AFR) AF: 0.0139 AC: 578 AN: 41580

American (AMR) AF: 0.00118 AC: 18 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00215 Hom.: 4

Bravo AF: 0.00445

ESP6500AA AF: 0.0141 AC: 62

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00131 AC: 159

Asia WGS AF: 0.000868 AC: 3 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0096	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.7
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.096
Sift	Benign	0.054	T
Sift4G	Benign	0.10	T
Polyphen		0.0090	B
Vest4		0.32
MVP		0.46
ClinPred		0.018	T
GERP RS		4.9
Varity_R		0.22
gMVP		0.56
Mutation Taster		=98/2	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: rs75546096; hg19: chr16-1891903;