rs374206181

Variant names:

• chr2-240481047-C-A
• rs374206181
• NM_001282771.3:c.2936G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-240481047-C-A
• chr2-240481047-C-G
• chr2-240481047-C-T

Variant summary

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

The NM_001282771.3(ANKMY1):​c.2936G>T​(p.Arg979Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,834 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R979H) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 33)
• Consequence: ANKMY1 NM_001282771.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.720
• Publications: 0 publications found

Genes affected

ANKMY1 (HGNC:20987): (ankyrin repeat and MYND domain containing 1) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282771.3. 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
	ANKMY1	NM_001282771.3	MANE Select	c.2936G>T	p.Arg979Leu	missense	Exon 17 of 18	NP_001269700.1	J3KQ21
	ANKMY1	NM_001354023.3		c.2936G>T	p.Arg979Leu	missense	Exon 18 of 19	NP_001340952.1	J3KQ21
	ANKMY1	NM_001393462.1		c.2852G>T	p.Arg951Leu	missense	Exon 17 of 18	NP_001380391.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKMY1	ENST00000401804.6	TSL:1 MANE Select	c.2936G>T	p.Arg979Leu	missense	Exon 17 of 18	ENSP00000385887.1	J3KQ21
	ANKMY1	ENST00000272972.7	TSL:1	c.2669G>T	p.Arg890Leu	missense	Exon 16 of 17	ENSP00000272972.3	Q9P2S6-1
	ANKMY1	ENST00000403283.6	TSL:1	c.2375G>T	p.Arg792Leu	missense	Exon 14 of 15	ENSP00000383968.1	J3KPY5

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151834 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151834 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74148

African (AFR) AF: 0.0000484 AC: 2 AN: 41320

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67926

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.0033	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.027
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.32	N
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.72
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.26
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.010	D
Polyphen		0.90	P
Vest4		0.39
MutPred		0.72		Loss of MoRF binding (P = 0.088)
MVP		0.79
ClinPred		0.95	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.48
Mutation Taster		=90/10	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: rs374206181; hg19: chr2-241420464;