7-16615806-G-T

Variant names:

• chr7-16615806-G-T
• NM_020319.3:c.469C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020319.3(ANKMY2):​c.469C>A​(p.Pro157Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. P157S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANKMY2 NM_020319.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.49

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKMY2	NM_020319.3	c.469C>A	p.Pro157Thr	missense_variant	Exon 5 of 10	ENST00000306999.7	NP_064715.1
LOC105375169	XR_007060225.1	n.222-220G>T		intron_variant	Intron 2 of 4
LOC105375169	XR_007060226.1	n.222-220G>T		intron_variant	Intron 2 of 4
LOC105375169	XR_007060227.1	n.81-220G>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKMY2	ENST00000306999.7	c.469C>A	p.Pro157Thr	missense_variant	Exon 5 of 10	1	NM_020319.3	ENSP00000303570.2
ANKMY2	ENST00000628652.1	c.469C>A	p.Pro157Thr	missense_variant	Exon 5 of 9	5		ENSP00000485738.1
ANKMY2	ENST00000447802.3	n.469C>A		non_coding_transcript_exon_variant	Exon 5 of 11	2		ENSP00000392259.1
ENSG00000287799	ENST00000663260.1	n.358-220G>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Uncertain	0.095	D
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-7.0	D;.
REVEL	Uncertain	0.52
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.99	D;.
Vest4		0.65
MutPred		0.34		Loss of catalytic residue at P157 (P = 0.0018);Loss of catalytic residue at P157 (P = 0.0018);
MVP		0.83
MPC		0.30
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.68
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-16655431;