22-43437863-T-C

Variant names:

• chr22-43437863-T-C
• rs135066
• NM_001044370.2:c.406+2648T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001044370.2(MPPED1):​c.406+2648T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 152,150 control chromosomes in the GnomAD database, including 51 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 0.021 (51 hom., cov: 33)
• Consequence: MPPED1 NM_001044370.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 1 publications found

Genes affected

MPPED1 (HGNC:1306): (metallophosphoesterase domain containing 1) Predicted to enable hydrolase activity. [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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0208 (3168/152150) while in subpopulation NFE AF = 0.031 (2108/67982). AF 95% confidence interval is 0.0299. There are 51 homozygotes in GnomAd4. There are 1448 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPPED1	NM_001044370.2	c.406+2648T>C		intron_variant	Intron 3 of 6	ENST00000443721.2	NP_001037835.1
MPPED1	NM_001362786.2	c.406+2648T>C		intron_variant	Intron 3 of 6		NP_001349715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPPED1	ENST00000443721.2	c.406+2648T>C		intron_variant	Intron 3 of 6	2	NM_001044370.2	ENSP00000400686.1
MPPED1	ENST00000417669.6	c.406+2648T>C		intron_variant	Intron 3 of 6	5		ENSP00000388137.1

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3163 AN: 152032 Hom.: 50 Cov.: 33

Gnomad AFR AF: 0.00979

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.00566

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0310

Gnomad OTH AF: 0.0244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0208 AC: 3168 AN: 152150 Hom.: 51 Cov.: 33 AF XY: 0.0195 AC XY: 1448 AN XY: 74380

African (AFR) AF: 0.00983 AC: 408 AN: 41500

American (AMR) AF: 0.0279 AC: 426 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 73 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00560 AC: 27 AN: 4818

European-Finnish (FIN) AF: 0.00566 AC: 60 AN: 10606

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0310 AC: 2108 AN: 67982

Other (OTH) AF: 0.0242 AC: 51 AN: 2108

Alfa AF: 0.0300 Hom.: 148

Bravo AF: 0.0232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
PhyloP100		-0.13

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs135066; hg19: chr22-43833782;