chr10-5883155-C-A

Position:

• chr10-5883155-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019046.3(ANKRD16):​c.700G>T​(p.Ala234Ser) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKRD16 NM_019046.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.01

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21732056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD16	NM_019046.3	c.700G>T	p.Ala234Ser	missense_variant	5/8	ENST00000380094.10
ANKRD16	NM_001009941.3	c.700G>T	p.Ala234Ser	missense_variant	5/7
ANKRD16	NM_001009943.3	c.700G>T	p.Ala234Ser	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD16	ENST00000380094.10	c.700G>T	p.Ala234Ser	missense_variant	5/8	2	NM_019046.3	P1
ANKRD16	ENST00000380092.8	c.700G>T	p.Ala234Ser	missense_variant	5/7	1		P1
ANKRD16	ENST00000191063.8	c.700G>T	p.Ala234Ser	missense_variant	5/6	3
ANKRD16	ENST00000492368.1	n.289G>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Jun 18, 2024

The c.700G>T (p.A234S) alteration is located in exon 5 (coding exon 5) of the ANKRD16 gene. This alteration results from a G to T substitution at nucleotide position 700, causing the alanine (A) at amino acid position 234 to be replaced by a serine (S). 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	Benign	0.11
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0038	T;T;.
Eigen	Benign	-0.013
Eigen_PC	Benign	0.0076
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.61	.;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.4	L;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.48	P;P;.
Vest4		0.25
MutPred		0.56		Gain of disorder (P = 0.0324);Gain of disorder (P = 0.0324);Gain of disorder (P = 0.0324);
MVP		0.69
MPC		0.32
ClinPred		0.60	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.44

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: chr10-5925118;