chr2-240480956-G-C

Variant names:

• chr2-240480956-G-C
• rs147804085
• NM_001282771.3:c.3027C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001282771.3(ANKMY1):​c.3027C>G​(p.Cys1009Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. C1009C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKMY1 NM_001282771.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 3 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.919

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.3027C>G	p.Cys1009Trp	missense	Exon 17 of 18	NP_001269700.1	J3KQ21
	ANKMY1	NM_001354023.3		c.3027C>G	p.Cys1009Trp	missense	Exon 18 of 19	NP_001340952.1	J3KQ21
	ANKMY1	NM_001393462.1		c.2943C>G	p.Cys981Trp	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.3027C>G	p.Cys1009Trp	missense	Exon 17 of 18	ENSP00000385887.1	J3KQ21
	ANKMY1	ENST00000272972.7	TSL:1	c.2760C>G	p.Cys920Trp	missense	Exon 16 of 17	ENSP00000272972.3	Q9P2S6-1
	ANKMY1	ENST00000403283.6	TSL:1	c.2466C>G	p.Cys822Trp	missense	Exon 14 of 15	ENSP00000383968.1	J3KPY5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.64	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		-0.37
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-8.6	D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.61		Loss of loop (P = 0.0073)
MVP		0.96
ClinPred		1.0	D
GERP RS		-1.5
Varity_R		0.92
gMVP		0.87
Mutation Taster		=71/29	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: rs147804085; hg19: chr2-241420373;