10-5884037-T-C

Variant names:

• chr10-5884037-T-C
• NM_019046.3:c.619A>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_019046.3(ANKRD16):​c.619A>G​(p.Thr207Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ANKRD16 NM_019046.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.44
• Publications: 0 publications found

Genes affected

ANKRD16 (HGNC:23471): (ankyrin repeat domain 16) Predicted to be involved in tRNA modification. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.979

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019046.3. 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
	ANKRD16	NM_019046.3	MANE Select	c.619A>G	p.Thr207Ala	missense	Exon 4 of 8	NP_061919.1	Q6P6B7-1
	ANKRD16	NM_001009941.3		c.619A>G	p.Thr207Ala	missense	Exon 4 of 7	NP_001009941.1	Q6P6B7-1
	ANKRD16	NM_001009943.3		c.619A>G	p.Thr207Ala	missense	Exon 4 of 6	NP_001009943.1	Q6P6B7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD16	ENST00000380094.10	TSL:2 MANE Select	c.619A>G	p.Thr207Ala	missense	Exon 4 of 8	ENSP00000369436.4	Q6P6B7-1
	ANKRD16	ENST00000380092.8	TSL:1	c.619A>G	p.Thr207Ala	missense	Exon 4 of 7	ENSP00000369434.4	Q6P6B7-1
	ANKRD16	ENST00000958073.1		c.640A>G	p.Thr214Ala	missense	Exon 4 of 8	ENSP00000628132.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		6.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.8	D
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.83		Gain of catalytic residue at T207 (P = 0.1356)
MVP		0.80
MPC		0.71
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.39
gMVP		0.80
Mutation Taster		=54/46	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

hg19: chr10-5926000;