17-73242948-G-T

Variant names:

• chr17-73242948-G-T
• rs1566290
• NM_001351264.2:c.1674G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001351264.2(MTNAP1):​c.1674G>T​(p.Thr558Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,613,134 control chromosomes in the GnomAD database, including 101,396 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 0.28 (7276 hom., cov: 32)
  • Exomes 𝑓: 0.35 (94120 hom.)
• Consequence: MTNAP1 NM_001351264.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46
• Publications: 27 publications found

Genes affected

MTNAP1 (HGNC:29601): (mitochondrial nucleoid associated protein 1) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CPSF4L (HGNC:33632): (cleavage and polyadenylation specific factor 4 like) Predicted to enable RNA binding activity and metal ion binding activity. Predicted to be involved in pre-mRNA cleavage required for polyadenylation. Predicted to be part of mRNA cleavage and polyadenylation specificity factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000265010 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-3.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTNAP1	NM_001351264.2	c.1674G>T	p.Thr558Thr	synonymous_variant	Exon 5 of 6	ENST00000535032.7	NP_001338193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTNAP1	ENST00000535032.7	c.1674G>T	p.Thr558Thr	synonymous_variant	Exon 5 of 6	1	NM_001351264.2	ENSP00000440551.2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42791 AN: 151934 Hom.: 7280 Cov.: 32

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.304

GnomAD2 exomes AF: 0.325 AC: 81595 AN: 250688 AF XY: 0.327

Gnomad AFR exome AF: 0.0823

Gnomad AMR exome AF: 0.378

Gnomad ASJ exome AF: 0.382

Gnomad EAS exome AF: 0.185

Gnomad FIN exome AF: 0.363

Gnomad NFE exome AF: 0.362

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.354 AC: 516547 AN: 1461082 Hom.: 94120 Cov.: 44 AF XY: 0.352 AC XY: 256077 AN XY: 726840

African (AFR) AF: 0.0765 AC: 2561 AN: 33466

American (AMR) AF: 0.380 AC: 16964 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 10028 AN: 26120

East Asian (EAS) AF: 0.178 AC: 7072 AN: 39694

South Asian (SAS) AF: 0.300 AC: 25895 AN: 86192

European-Finnish (FIN) AF: 0.365 AC: 19454 AN: 53296

Middle Eastern (MID) AF: 0.281 AC: 1614 AN: 5744

European-Non Finnish (NFE) AF: 0.371 AC: 412554 AN: 1111566

Other (OTH) AF: 0.338 AC: 20405 AN: 60360

GnomAD4 genome AF: 0.281 AC: 42791 AN: 152052 Hom.: 7276 Cov.: 32 AF XY: 0.282 AC XY: 20963 AN XY: 74308

African (AFR) AF: 0.0889 AC: 3689 AN: 41486

American (AMR) AF: 0.370 AC: 5660 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1320 AN: 3472

East Asian (EAS) AF: 0.184 AC: 950 AN: 5174

South Asian (SAS) AF: 0.294 AC: 1414 AN: 4816

European-Finnish (FIN) AF: 0.356 AC: 3754 AN: 10556

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24941 AN: 67954

Other (OTH) AF: 0.301 AC: 634 AN: 2108

Alfa AF: 0.328 Hom.: 13394

Bravo AF: 0.271

Asia WGS AF: 0.214 AC: 748 AN: 3478

EpiCase AF: 0.355

EpiControl AF: 0.357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.13
DANN	Benign	0.82
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1566290; hg19: chr17-71239087; COSMIC: COSV52145567; COSMIC: COSV52145567;