4-99062161-T-C

Variant names:

• chr4-99062161-T-C
• rs1238741
• NM_015143.3:c.*844T>C

Variant summary

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

The NM_015143.3(METAP1):​c.*844T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,166 control chromosomes in the GnomAD database, including 6,503 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 0.24 (6503 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: METAP1 NM_015143.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.964
• Publications: 12 publications found

Genes affected

METAP1 (HGNC:15789): (methionyl aminopeptidase 1) Predicted to enable aminopeptidase activity and metalloexopeptidase activity. Involved in platelet aggregation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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 (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METAP1	NM_015143.3	c.*844T>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000296411.11	NP_055958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METAP1	ENST00000296411.11	c.*844T>C		3_prime_UTR_variant	Exon 11 of 11	1	NM_015143.3	ENSP00000296411.6
METAP1	ENST00000514051.1	c.*844T>C		downstream_gene_variant		1		ENSP00000422689.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36658 AN: 152048 Hom.: 6491 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.213

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.241 AC: 36711 AN: 152166 Hom.: 6503 Cov.: 32 AF XY: 0.247 AC XY: 18342 AN XY: 74406

African (AFR) AF: 0.406 AC: 16844 AN: 41492

American (AMR) AF: 0.282 AC: 4302 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 460 AN: 3470

East Asian (EAS) AF: 0.797 AC: 4117 AN: 5166

South Asian (SAS) AF: 0.133 AC: 644 AN: 4834

European-Finnish (FIN) AF: 0.179 AC: 1895 AN: 10602

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7895 AN: 68002

Other (OTH) AF: 0.215 AC: 455 AN: 2112

Alfa AF: 0.163 Hom.: 9357

Bravo AF: 0.264

Asia WGS AF: 0.421 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.2
DANN	Benign	0.68
PhyloP100		0.96
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: rs1238741; hg19: chr4-99983312;