13-110879666-C-A

Variant names:

• chr13-110879666-C-A
• rs750585921
• NM_017664.4:c.1234G>T

Variant summary

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

The NM_017664.4(ANKRD10):​c.1234G>T​(p.Gly412Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: ANKRD10 NM_017664.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10

Genes affected

ANKRD10 (HGNC:20265): (ankyrin repeat domain 10)

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, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD10	NM_017664.4	c.1234G>T	p.Gly412Cys	missense_variant	Exon 6 of 6	ENST00000267339.6	NP_060134.2
ANKRD10	XM_024449380.2	c.*431G>T		3_prime_UTR_variant	Exon 6 of 6		XP_024305148.1
ANKRD10	NR_104587.2	n.1431G>T		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD10	ENST00000267339.6	c.1234G>T	p.Gly412Cys	missense_variant	Exon 6 of 6	2	NM_017664.4	ENSP00000267339.2
ANKRD10	ENST00000485844.1	n.*102G>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74364

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1234G>T (p.G412C) alteration is located in exon 6 (coding exon 6) of the ANKRD10 gene. This alteration results from a G to T substitution at nucleotide position 1234, causing the glycine (G) at amino acid position 412 to be replaced by a cysteine (C). 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	0.20
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.0073	D
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.42		Gain of helix (P = 0.0022);
MVP		0.84
MPC		1.1
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.42
gMVP		0.46

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

LitVar

Other links and lift over

dbSNP: rs750585921; hg19: chr13-111532013;