2-127873991-C-G

Variant names:

• chr2-127873991-C-G
• rs146751577
• NM_001199140.2:c.244G>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001199140.2(AMMECR1L):​c.244G>C​(p.Ala82Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,614,202 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0085 (8 hom., cov: 32)
  • Exomes 𝑓: 0.012 (142 hom.)
• Consequence: AMMECR1L NM_001199140.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.935
• Publications: 9 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047555566).
• BP6: Variant 2-127873991-C-G is Benign according to our data. Variant chr2-127873991-C-G is described in ClinVar as Benign. ClinVar VariationId is 769573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1291 AD gene.

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.244G>C	p.Ala82Pro	missense	Exon 3 of 8	NP_001186069.1	Q6DCA0
	AMMECR1L	NM_001410953.1		c.244G>C	p.Ala82Pro	missense	Exon 3 of 9	NP_001397882.1	A0A7P0Z454
	AMMECR1L	NM_031445.2		c.244G>C	p.Ala82Pro	missense	Exon 3 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.244G>C	p.Ala82Pro	missense	Exon 3 of 8	ENSP00000272647.6	Q6DCA0
	AMMECR1L	ENST00000393001.1	TSL:1	c.244G>C	p.Ala82Pro	missense	Exon 3 of 8	ENSP00000376726.1	Q6DCA0
	AMMECR1L	ENST00000681844.1		c.244G>C	p.Ala82Pro	missense	Exon 3 of 9	ENSP00000505104.1	A0A7P0Z454

Frequencies

GnomAD3 genomes AF: 0.00849 AC: 1292 AN: 152194 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00179

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00811 AC: 2039 AN: 251476 AF XY: 0.00817

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00546

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0116

Gnomad NFE exome AF: 0.0118

Gnomad OTH exome AF: 0.00945

GnomAD4 exome AF: 0.0119 AC: 17448 AN: 1461890 Hom.: 142 Cov.: 32 AF XY: 0.0118 AC XY: 8568 AN XY: 727248

African (AFR) AF: 0.00140 AC: 47 AN: 33480

American (AMR) AF: 0.00517 AC: 231 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00594 AC: 512 AN: 86258

European-Finnish (FIN) AF: 0.0108 AC: 575 AN: 53420

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5766

European-Non Finnish (NFE) AF: 0.0139 AC: 15405 AN: 1112010

Other (OTH) AF: 0.0110 AC: 664 AN: 60396

GnomAD4 genome AF: 0.00848 AC: 1291 AN: 152312 Hom.: 8 Cov.: 32 AF XY: 0.00846 AC XY: 630 AN XY: 74470

African (AFR) AF: 0.00178 AC: 74 AN: 41564

American (AMR) AF: 0.00889 AC: 136 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4826

European-Finnish (FIN) AF: 0.0121 AC: 128 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0130 AC: 886 AN: 68030

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00970 Hom.: 7

Bravo AF: 0.00822

TwinsUK AF: 0.0129 AC: 48

ALSPAC AF: 0.0135 AC: 52

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.0135 AC: 116

ExAC AF: 0.00788 AC: 957

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0120

EpiControl AF: 0.0113

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.94
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.027
Sift	Benign	0.12	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.17
MVP		0.11
MPC		0.45
ClinPred		0.023	T
GERP RS		3.3
Varity_R		0.067
gMVP		0.73
Mutation Taster		=98/2	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: rs146751577; hg19: chr2-128631565; COSMIC: COSV108010267;