2-127865150-G-C

Variant names:

• chr2-127865150-G-C
• NM_001199140.2:c.877C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001199140.2(AMMECR1L):​c.877C>G​(p.His293Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMMECR1L NM_001199140.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30296063).

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.877C>G	p.His293Asp	missense	Exon 8 of 8	NP_001186069.1	Q6DCA0
	AMMECR1L	NM_001410953.1		c.1012C>G	p.His338Asp	missense	Exon 9 of 9	NP_001397882.1	A0A7P0Z454
	AMMECR1L	NM_031445.2		c.877C>G	p.His293Asp	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.877C>G	p.His293Asp	missense	Exon 8 of 8	ENSP00000272647.6	Q6DCA0
	AMMECR1L	ENST00000393001.1	TSL:1	c.877C>G	p.His293Asp	missense	Exon 8 of 8	ENSP00000376726.1	Q6DCA0
	AMMECR1L	ENST00000681844.1		c.1012C>G	p.His338Asp	missense	Exon 9 of 9	ENSP00000505104.1	A0A7P0Z454

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.2	L
PhyloP100		9.6
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.30
Sift	Benign	0.068	T
Sift4G	Uncertain	0.018	D
Polyphen		0.24	B
Vest4		0.59
MutPred		0.36		Loss of catalytic residue at C294 (P = 0.0627)
MVP		0.20
MPC		0.82
ClinPred		0.94	D
GERP RS		5.9
Varity_R		0.25
gMVP		0.73
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr2-128622724;