2-127873910-A-C

Position:

• chr2-127873910-A-C

Variant summary

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

The NM_001199140.2(AMMECR1L):​c.325T>G​(p.Cys109Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: AMMECR1L NM_001199140.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.90

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMMECR1L	NM_001199140.2	c.325T>G	p.Cys109Gly	missense_variant	3/8	ENST00000272647.10	NP_001186069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMMECR1L	ENST00000272647.10	c.325T>G	p.Cys109Gly	missense_variant	3/8	1	NM_001199140.2	ENSP00000272647.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251484 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135916

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.325T>G (p.C109G) alteration is located in exon 3 (coding exon 1) of the AMMECR1L gene. This alteration results from a T to G substitution at nucleotide position 325, causing the cysteine (C) at amino acid position 109 to be replaced by a glycine (G). 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	0.31
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.0046	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Benign	0.20
Sift	Benign	0.30	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.091	B;B
Vest4		0.72
MutPred		0.67		Loss of helix (P = 0.0795);Loss of helix (P = 0.0795);
MVP		0.23
MPC		1.9
ClinPred		0.52	D
GERP RS		5.4
Varity_R		0.41
gMVP		0.98

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

LitVar

Other links and lift over

dbSNP: rs1350098189; hg19: chr2-128631484;