chr17-73242948-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001351264.2(MTNAP1):​c.1674G>C​(p.Thr558Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,548 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-3.46 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351264.2. 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
	MTNAP1	NM_001351264.2	MANE Select	c.1674G>C	p.Thr558Thr	synonymous	Exon 5 of 6	NP_001338193.2
	MTNAP1	NM_017941.6		c.1674G>C	p.Thr558Thr	synonymous	Exon 5 of 6	NP_060411.3
	MTNAP1	NM_001100622.4		c.1674G>C	p.Thr558Thr	synonymous	Exon 5 of 6	NP_001094092.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNAP1	ENST00000535032.7	TSL:1 MANE Select	c.1674G>C	p.Thr558Thr	synonymous	Exon 5 of 6	ENSP00000440551.2
	MTNAP1	ENST00000268942.12	TSL:1	c.1566G>C	p.Thr522Thr	synonymous	Exon 4 of 5	ENSP00000268942.8
	MTNAP1	ENST00000359042.6	TSL:5	c.1674G>C	p.Thr558Thr	synonymous	Exon 5 of 6	ENSP00000351937.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250688 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461548 Hom.: 0 Cov.: 44 AF XY: 0.00000138 AC XY: 1 AN XY: 727068

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111882

Other (OTH) AF: 0.00 AC: 0 AN: 60382

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.10
DANN	Benign	0.75
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;