13-110879702-C-G

Variant names:

• chr13-110879702-C-G
• NM_017664.4:c.1198G>C

Variant summary

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

The NM_017664.4(ANKRD10):​c.1198G>C​(p.Val400Leu) 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. 13/21 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: ANKRD10 NM_017664.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.11

Genes affected

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

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=0.26315182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD10	NM_017664.4	c.1198G>C	p.Val400Leu	missense_variant	Exon 6 of 6	ENST00000267339.6	NP_060134.2
ANKRD10	XM_024449380.2	c.*395G>C		3_prime_UTR_variant	Exon 6 of 6		XP_024305148.1
ANKRD10	NR_104587.2	n.1395G>C		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.1198G>C	p.Val400Leu	missense_variant	Exon 6 of 6	2	NM_017664.4	ENSP00000267339.2
ANKRD10	ENST00000485844.1	n.*66G>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1198G>C (p.V400L) alteration is located in exon 6 (coding exon 6) of the ANKRD10 gene. This alteration results from a G to C substitution at nucleotide position 1198, causing the valine (V) at amino acid position 400 to be replaced by a leucine (L). 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	0.14
BayesDel_addAF	Benign	0.0023	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.046
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.20	T
Polyphen		0.79	P
Vest4		0.33
MutPred		0.28		Gain of loop (P = 0.0045);
MVP		0.73
MPC		0.52
ClinPred		0.69	D
GERP RS		4.0
Varity_R		0.10
gMVP		0.36

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: chr13-111532049;