17-50517407-C-A

Variant names:

• chr17-50517407-C-A
• rs773750865
• NM_032133.6:c.319C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032133.6(MYCBPAP):​c.319C>A​(p.Arg107Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R107C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MYCBPAP NM_032133.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09269655).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCBPAP	NM_032133.6	MANE Select	c.319C>A	p.Arg107Ser	missense	Exon 3 of 19	NP_115509.5
	MYCBPAP	NM_001366294.2		c.319C>A	p.Arg107Ser	missense	Exon 3 of 19	NP_001353223.1	C9JXR6
	MYCBPAP	NR_158785.2		n.555C>A		non_coding_transcript_exon	Exon 3 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCBPAP	ENST00000323776.11	TSL:1 MANE Select	c.319C>A	p.Arg107Ser	missense	Exon 3 of 19	ENSP00000323184.6	Q8TBZ2-2
	MYCBPAP	ENST00000452039.7	TSL:5	c.319C>A	p.Arg107Ser	missense	Exon 3 of 19	ENSP00000407145.3	C9JXR6
	MYCBPAP	ENST00000879749.1		c.319C>A	p.Arg107Ser	missense	Exon 3 of 19	ENSP00000549808.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.0
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.053
Sift	Benign	0.069	T
Sift4G	Benign	0.079	T
Vest4		0.31
MutPred		0.32		Gain of glycosylation at R113 (P = 0.0297)
MVP		0.20
MPC		0.29
ClinPred		0.34	T
GERP RS		2.3

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: rs773750865; hg19: chr17-48594768;