NM_020319.3:c.1171G>T

Variant names:

• chr7-16600916-C-A
• rs770307031
• NM_020319.3:c.1171G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020319.3(ANKMY2):​c.1171G>T​(p.Val391Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. V391I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ANKMY2 NM_020319.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 2 publications found

Genes affected

ANKMY2 (HGNC:25370): (ankyrin repeat and MYND domain containing 2) Predicted to enable enzyme binding activity and metal ion binding activity. Predicted to be located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000287799 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06542328).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020319.3. 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
	ANKMY2	NM_020319.3	MANE Select	c.1171G>T	p.Val391Phe	missense	Exon 10 of 10	NP_064715.1	Q8IV38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKMY2	ENST00000306999.7	TSL:1 MANE Select	c.1171G>T	p.Val391Phe	missense	Exon 10 of 10	ENSP00000303570.2	Q8IV38
	ANKMY2	ENST00000949063.1		c.1369G>T	p.Val457Phe	missense	Exon 11 of 11	ENSP00000619122.1
	ANKMY2	ENST00000949062.1		c.1252G>T	p.Val418Phe	missense	Exon 11 of 11	ENSP00000619121.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454748 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723674

African (AFR) AF: 0.00 AC: 0 AN: 33088

American (AMR) AF: 0.00 AC: 0 AN: 42890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25746

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39594

South Asian (SAS) AF: 0.00 AC: 0 AN: 85022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109286

Other (OTH) AF: 0.00 AC: 0 AN: 60084

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.010
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.24
Sift	Uncertain	0.021	D
Sift4G	Benign	0.28	T
Polyphen		0.26	B
Vest4		0.20
MutPred		0.10		Gain of catalytic residue at V391 (P = 0.1098)
MVP		0.56
MPC		0.053
ClinPred		0.14	T
GERP RS		1.3
Varity_R		0.073
gMVP		0.26
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs770307031; hg19: chr7-16640541;