17-50508582-C-T

Variant names:

• chr17-50508582-C-T
• rs770658579
• NM_032133.6:c.-93C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032133.6(MYCBPAP):​c.-93C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000285 in 1,401,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: MYCBPAP NM_032133.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.432

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19035155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYCBPAP	NM_032133.6	c.-93C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 19	ENST00000323776.11	NP_115509.5
MYCBPAP	NM_032133.6	c.-93C>T		5_prime_UTR_variant	Exon 1 of 19	ENST00000323776.11	NP_115509.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYCBPAP	ENST00000323776	c.-93C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 19	1	NM_032133.6	ENSP00000323184.6
MYCBPAP	ENST00000323776	c.-93C>T		5_prime_UTR_variant	Exon 1 of 19	1	NM_032133.6	ENSP00000323184.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000285 AC: 4 AN: 1401306 Hom.: 0 Cov.: 31 AF XY: 0.00000433 AC XY: 3 AN XY: 692230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000370

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.37C>T (p.R13C) alteration is located in exon 1 (coding exon 1) of the MYCBPAP gene. This alteration results from a C to T substitution at nucleotide position 37, causing the arginine (R) at amino acid position 13 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0054	.;.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.69	T;.;.
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.72	N;D;N
REVEL	Benign	0.11
Sift	Uncertain	0.025	D;D;D
Sift4G	Benign	0.070	T;D;D
Vest4		0.13
MutPred		0.41		Loss of MoRF binding (P = 0.0202);Loss of MoRF binding (P = 0.0202);Loss of MoRF binding (P = 0.0202);
MVP		0.56
MPC		0.24
ClinPred		0.88	D
GERP RS		1.8

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

Publications

LitVar

Other links and lift over

dbSNP: rs770658579; hg19: chr17-48585943;