11-67290444-C-G

Variant names:

• chr11-67290444-C-G
• rs532670227
• NM_207354.3:c.349C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207354.3(ANKRD13D):​c.349C>G​(p.Gln117Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000038 in 1,577,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ANKRD13D NM_207354.3 missense, splice_region
• Scores: Splicing: ADA: 0.04797
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.582
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030339211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD13D	NM_207354.3	c.349C>G	p.Gln117Glu	missense_variant, splice_region_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.349C>G	p.Gln117Glu	missense_variant, splice_region_variant	Exon 3 of 15	1	NM_207354.3	ENSP00000427130.2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152184 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000104 AC: 2 AN: 192452 AF XY: 0.0000195

Gnomad AFR exome AF: 0.0000861

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1424918 Hom.: 0 Cov.: 31 AF XY: 0.00000284 AC XY: 2 AN XY: 704972

African (AFR) AF: 0.00 AC: 0 AN: 32994

American (AMR) AF: 0.00 AC: 0 AN: 38706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25368

East Asian (EAS) AF: 0.00 AC: 0 AN: 38404

South Asian (SAS) AF: 0.00 AC: 0 AN: 81330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4120

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1094386

Other (OTH) AF: 0.00 AC: 0 AN: 58942

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152302 Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3 AN XY: 74464

African (AFR) AF: 0.0000241 AC: 1 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000167 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.349C>G (p.Q117E) alteration is located in exon 3 (coding exon 3) of the ANKRD13D gene. This alteration results from a C to G substitution at nucleotide position 349, causing the glutamine (Q) at amino acid position 117 to be replaced by a glutamic acid (E). 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	0.075
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	23
DANN	Benign	0.77
DEOGEN2	Benign	0.023	T;.;T;T;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.94	.;D;.;D;D
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.030	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.68	N;.;N;N;.
PhyloP100		0.58
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.24	N;N;N;N;.
REVEL	Benign	0.093
Sift	Benign	1.0	T;T;T;T;.
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0020	B;B;B;B;.
Vest4		0.20
MVP		0.15
MPC		0.58
ClinPred		0.017	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.15
gMVP		0.38
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.048
dbscSNV1_RF	Benign	0.37
SpliceAI score (max)		0.17		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

dbSNP: rs532670227; hg19: chr11-67057915;