11-67290435-A-C

Variant names:

• chr11-67290435-A-C
• NM_207354.3:c.340A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_207354.3(ANKRD13D):​c.340A>C​(p.Lys114Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K114N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ANKRD13D NM_207354.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.26
• Publications: 0 publications found

Genes affected

ANKRD13D (HGNC:27880): (ankyrin repeat domain 13D) The protein encoded by this gene is a member of the ankyrin repeat domain (ANKRD) 13 family, which currently consists of four proteins containing ubiquitin-interacting motifs. These proteins are integral membrane proteins that bind specifically to Lys-63-linked ubiquitin chains on membrane-bound proteins, targeting those proteins for rapid internalization. [provided by RefSeq, Dec 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD13D	NM_207354.3	c.340A>C	p.Lys114Gln	missense_variant	Exon 3 of 15	ENST00000511455.7	NP_997237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD13D	ENST00000511455.7	c.340A>C	p.Lys114Gln	missense_variant	Exon 3 of 15	1	NM_207354.3	ENSP00000427130.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.340A>C (p.K114Q) alteration is located in exon 3 (coding exon 3) of the ANKRD13D gene. This alteration results from a A to C substitution at nucleotide position 340, causing the lysine (K) at amino acid position 114 to be replaced by a glutamine (Q). 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	Benign	0.0019	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.;T;T;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D;.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.42	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.;L;L;.
PhyloP100		9.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.2	D;D;D;D;.
REVEL	Benign	0.26
Sift	Benign	0.034	D;T;D;D;.
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		0.38	B;P;B;B;.
Vest4		0.68
MutPred		0.32		Loss of ubiquitination at K27 (P = 0.0326);.;Loss of ubiquitination at K27 (P = 0.0326);Loss of ubiquitination at K27 (P = 0.0326);Loss of ubiquitination at K27 (P = 0.0326);
MVP		0.21
MPC		1.2
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.56
gMVP		0.66
Mutation Taster		=65/35	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: chr11-67057906;