2-127874140-T-C

Variant names:

• chr2-127874140-T-C
• NM_001199140.2:c.95A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001199140.2(AMMECR1L):​c.95A>G​(p.His32Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMMECR1L NM_001199140.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10788381).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMMECR1L	NM_001199140.2	c.95A>G	p.His32Arg	missense_variant	Exon 3 of 8	ENST00000272647.10	NP_001186069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMMECR1L	ENST00000272647.10	c.95A>G	p.His32Arg	missense_variant	Exon 3 of 8	1	NM_001199140.2	ENSP00000272647.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.95A>G (p.H32R) alteration is located in exon 3 (coding exon 1) of the AMMECR1L gene. This alteration results from a A to G substitution at nucleotide position 95, causing the histidine (H) at amino acid position 32 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.080
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.86	.;D
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.66	N;N
REVEL	Benign	0.025
Sift	Benign	0.13	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.016	B;B
Vest4		0.26
MutPred		0.25		Gain of MoRF binding (P = 0.0052);Gain of MoRF binding (P = 0.0052);
MVP		0.11
MPC		0.43
ClinPred		0.51	D
GERP RS		5.5
Varity_R		0.16
gMVP		0.57

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-128631714;