chr2-199961847-C-CT

Variant names:

• chr2-199961847-C-CT
• rs554643599
• NM_001394955.1:c.719dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001394955.1(MAIP1):​c.719dupT​(p.Leu240PhefsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000597 in 1,613,988 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (7 hom.)
• Consequence: MAIP1 NM_001394955.1 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.266
• Publications: 0 publications found

Genes affected

MAIP1 (HGNC:26198): (matrix AAA peptidase interacting protein 1) Predicted to enable ribosome binding activity. Involved in calcium import into the mitochondrion; mitochondrial calcium ion homeostasis; and protein insertion into mitochondrial membrane. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 2-199961847-C-CT is Benign according to our data. Variant chr2-199961847-C-CT is described in ClinVar as Likely_benign. ClinVar VariationId is 3898234.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000529 (773/1461668) while in subpopulation AMR AF = 0.0162 (724/44714). AF 95% confidence interval is 0.0152. There are 7 homozygotes in GnomAdExome4. There are 312 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394955.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAIP1	NM_001394955.1	MANE Select	c.719dupT	p.Leu240PhefsTer10	frameshift	Exon 4 of 5	NP_001381884.1	Q8WWC4
	MAIP1	NM_024520.3		c.719dupT	p.Leu240PhefsTer10	frameshift	Exon 5 of 6	NP_078796.2	Q8WWC4
	MAIP1	NM_001369399.1		c.650-1883dupT		intron	N/A	NP_001356328.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAIP1	ENST00000392290.6	TSL:1 MANE Select	c.719dupT	p.Leu240PhefsTer10	frameshift	Exon 4 of 5	ENSP00000376111.1	Q8WWC4
	MAIP1	ENST00000295079.6	TSL:2	c.719dupT	p.Leu240PhefsTer10	frameshift	Exon 5 of 6	ENSP00000295079.2	Q8WWC4
	MAIP1	ENST00000435773.2	TSL:3	c.625+1970dupT		intron	N/A	ENSP00000396846.2	H7C0V0

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 192 AN: 152202 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00238 AC: 599 AN: 251368 AF XY: 0.00179

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0168

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000489

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000529 AC: 773 AN: 1461668 Hom.: 7 Cov.: 30 AF XY: 0.000429 AC XY: 312 AN XY: 727136

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.0162 AC: 724 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111862

Other (OTH) AF: 0.000679 AC: 41 AN: 60388

GnomAD4 genome AF: 0.00125 AC: 190 AN: 152320 Hom.: 2 Cov.: 32 AF XY: 0.00132 AC XY: 98 AN XY: 74480

African (AFR) AF: 0.000216 AC: 9 AN: 41578

American (AMR) AF: 0.0115 AC: 176 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000274 Hom.: 0

Bravo AF: 0.00218

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.27
Mutation Taster		=176/24	polymorphism

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: rs554643599; hg19: chr2-200826570;