17-50513848-A-G

Variant names:

• chr17-50513848-A-G
• rs6504663
• NM_032133.6:c.77-2722A>G

Variant summary

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

The NM_032133.6(MYCBPAP):​c.77-2722A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,058 control chromosomes in the GnomAD database, including 11,854 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 0.35 (11854 hom., cov: 32)
• Consequence: MYCBPAP NM_032133.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215
• Publications: 17 publications found

Genes affected

MYCBPAP (HGNC:19677): (MYCBP associated protein) Involved in spermatogenesis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MYCBPAP Gene-Disease associations (from GenCC):

• spermatogenic failure

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032133.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCBPAP	NM_032133.6	MANE Select	c.77-2722A>G		intron	N/A	NP_115509.5
	MYCBPAP	NM_001366294.2		c.77-2722A>G		intron	N/A	NP_001353223.1
	MYCBPAP	NR_158785.2		n.313-2722A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCBPAP	ENST00000323776.11	TSL:1 MANE Select	c.77-2722A>G		intron	N/A	ENSP00000323184.6
	MYCBPAP	ENST00000452039.7	TSL:5	c.77-2722A>G		intron	N/A	ENSP00000407145.3
	MYCBPAP	ENST00000458692.2	TSL:5	c.77-997A>G		intron	N/A	ENSP00000397686.2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52452 AN: 151936 Hom.: 11810 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.316

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.346 AC: 52561 AN: 152058 Hom.: 11854 Cov.: 32 AF XY: 0.341 AC XY: 25359 AN XY: 74348

African (AFR) AF: 0.637 AC: 26402 AN: 41448

American (AMR) AF: 0.335 AC: 5118 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1446 AN: 3468

East Asian (EAS) AF: 0.111 AC: 576 AN: 5168

South Asian (SAS) AF: 0.187 AC: 904 AN: 4822

European-Finnish (FIN) AF: 0.191 AC: 2022 AN: 10588

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.221 AC: 15011 AN: 67988

Other (OTH) AF: 0.324 AC: 683 AN: 2110

Alfa AF: 0.257 Hom.: 16697

Bravo AF: 0.377

Asia WGS AF: 0.221 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	7.6
DANN	Benign	0.75
PhyloP100		0.21
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: rs6504663; hg19: chr17-48591209;