17-50508193-T-C

Variant names:

• chr17-50508193-T-C
• rs73351675
• XM_047436908.1:c.142+93T>C

Variant summary

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

The XM_047436908.1(MYCBPAP):​c.142+93T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 238,362 control chromosomes in the GnomAD database, including 35,388 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 0.55 (25935 hom., cov: 32)
  • Exomes 𝑓: 0.46 (9453 hom.)
• Consequence: MYCBPAP XM_047436908.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 8 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

ENSG00000249451 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000323776.11. 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
	MYCBPAP	NM_032133.6	MANE Select	c.-482T>C		upstream_gene	N/A	NP_115509.5
	MYCBPAP	NM_001366294.2		c.-482T>C		upstream_gene	N/A	NP_001353223.1	C9JXR6
	MYCBPAP	NR_158785.2		n.-246T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000249451	ENST00000502300.1	TSL:5	n.27+109A>G		intron	N/A
	MYCBPAP	ENST00000323776.11	TSL:1 MANE Select	c.-482T>C		upstream_gene	N/A	ENSP00000323184.6	Q8TBZ2-2
	MYCBPAP	ENST00000879749.1		c.-482T>C		upstream_gene	N/A	ENSP00000549808.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83870 AN: 151934 Hom.: 25864 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.503

GnomAD4 exome AF: 0.458 AC: 39504 AN: 86310 Hom.: 9453 AF XY: 0.459 AC XY: 20547 AN XY: 44748

African (AFR) AF: 0.861 AC: 1296 AN: 1506

American (AMR) AF: 0.576 AC: 590 AN: 1024

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1482 AN: 2650

East Asian (EAS) AF: 0.267 AC: 702 AN: 2632

South Asian (SAS) AF: 0.451 AC: 4538 AN: 10052

European-Finnish (FIN) AF: 0.461 AC: 2650 AN: 5744

Middle Eastern (MID) AF: 0.479 AC: 205 AN: 428

European-Non Finnish (NFE) AF: 0.447 AC: 25346 AN: 56664

Other (OTH) AF: 0.480 AC: 2695 AN: 5610

GnomAD4 genome AF: 0.552 AC: 84008 AN: 152052 Hom.: 25935 Cov.: 32 AF XY: 0.548 AC XY: 40724 AN XY: 74362

African (AFR) AF: 0.847 AC: 35159 AN: 41500

American (AMR) AF: 0.524 AC: 8015 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1881 AN: 3468

East Asian (EAS) AF: 0.221 AC: 1134 AN: 5136

South Asian (SAS) AF: 0.398 AC: 1921 AN: 4828

European-Finnish (FIN) AF: 0.457 AC: 4841 AN: 10586

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29415 AN: 67926

Other (OTH) AF: 0.509 AC: 1075 AN: 2112

Alfa AF: 0.502 Hom.: 2605

Bravo AF: 0.574

Asia WGS AF: 0.372 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.59
PhyloP100		-1.4
PromoterAI		-0.32	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs73351675; hg19: chr17-48585554;