10-5884037-T-C

Position:

• chr10-5884037-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 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

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD16	NM_019046.3	c.619A>G	p.Thr207Ala	missense_variant	4/8	ENST00000380094.10
ANKRD16	NM_001009941.3	c.619A>G	p.Thr207Ala	missense_variant	4/7
ANKRD16	NM_001009943.3	c.619A>G	p.Thr207Ala	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD16	ENST00000380094.10	c.619A>G	p.Thr207Ala	missense_variant	4/8	2	NM_019046.3	P1
ANKRD16	ENST00000380092.8	c.619A>G	p.Thr207Ala	missense_variant	4/7	1		P1
ANKRD16	ENST00000191063.8	c.619A>G	p.Thr207Ala	missense_variant	4/6	3
ANKRD16	ENST00000492368.1	n.208A>G		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2024

The c.619A>G (p.T207A) alteration is located in exon 4 (coding exon 4) of the ANKRD16 gene. This alteration results from a A to G substitution at nucleotide position 619, causing the threonine (T) at amino acid position 207 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Pathogenic	3.1	M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.8	D;D;D
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.017	D;D;T
Polyphen		1.0	D;D;.
Vest4		0.84
MutPred		0.83		Gain of catalytic residue at T207 (P = 0.1356);Gain of catalytic residue at T207 (P = 0.1356);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

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: chr10-5926000;