2-127865169-C-G

Variant names:

• chr2-127865169-C-G
• NM_001199140.2:c.858G>C
• AMMECR1L p.Glu286Asp

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001199140.2(AMMECR1L):​c.858G>C​(p.Glu286Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMMECR1L NM_001199140.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 0 publications found

Genes affected

AMMECR1L (HGNC:28658): (AMMECR1 like) Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LOC107985803 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14275625).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199140.2. 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
	AMMECR1L	NM_001199140.2	MANE Select	c.858G>C	p.Glu286Asp	missense	Exon 8 of 8	NP_001186069.1	Q6DCA0
	AMMECR1L	NM_001410953.1		c.993G>C	p.Glu331Asp	missense	Exon 9 of 9	NP_001397882.1	A0A7P0Z454
	AMMECR1L	NM_031445.2		c.858G>C	p.Glu286Asp	missense	Exon 8 of 8	NP_113633.2	Q6DCA0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMMECR1L	ENST00000272647.10	TSL:1 MANE Select	c.858G>C	p.Glu286Asp	missense	Exon 8 of 8	ENSP00000272647.6	Q6DCA0
	AMMECR1L	ENST00000393001.1	TSL:1	c.858G>C	p.Glu286Asp	missense	Exon 8 of 8	ENSP00000376726.1	Q6DCA0
	AMMECR1L	ENST00000681844.1		c.993G>C	p.Glu331Asp	missense	Exon 9 of 9	ENSP00000505104.1	A0A7P0Z454

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	7.3
DANN	Benign	0.96
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.77	N
PhyloP100		-0.30
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.18
Sift	Benign	0.25	T
Sift4G	Benign	0.38	T
Varity_R		0.13
gMVP		0.76
Mutation Taster		=73/27	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-128622743;