11-67291653-C-T

Variant names:

• chr11-67291653-C-T
• rs370375085
• NM_207354.3:c.448C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_207354.3(ANKRD13D):​c.448C>T​(p.Arg150Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00007 in 1,614,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R150Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: ANKRD13D NM_207354.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.753
• Publications: 2 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07605839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD13D	NM_207354.3	c.448C>T	p.Arg150Trp	missense_variant	Exon 5 of 15	ENST00000511455.7	NP_997237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD13D	ENST00000511455.7	c.448C>T	p.Arg150Trp	missense_variant	Exon 5 of 15	1	NM_207354.3	ENSP00000427130.2

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000756 AC: 19 AN: 251252 AF XY: 0.0000736

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000513 AC: 75 AN: 1461766 Hom.: 0 Cov.: 33 AF XY: 0.0000495 AC XY: 36 AN XY: 727184

African (AFR) AF: 0.00116 AC: 39 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1112004

Other (OTH) AF: 0.000149 AC: 9 AN: 60394

GnomAD4 genome AF: 0.000250 AC: 38 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74458

African (AFR) AF: 0.000866 AC: 36 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000541 Hom.: 0

Bravo AF: 0.000253

ESP6500AA AF: 0.000682 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000123 AC: 15

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.448C>T (p.R150W) alteration is located in exon 5 (coding exon 5) of the ANKRD13D gene. This alteration results from a C to T substitution at nucleotide position 448, causing the arginine (R) at amino acid position 150 to be replaced by a tryptophan (W). 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	0.32
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	T;.;T;T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.99	.;D;.;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.076	T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L;.;L;L;.
PhyloP100		0.75
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.6	D;D;D;D;.
REVEL	Benign	0.084
Sift	Uncertain	0.011	D;D;D;D;.
Sift4G	Uncertain	0.015	D;D;D;D;D
Polyphen		1.0	D;D;D;D;.
Vest4		0.64
MVP		0.23
MPC		1.2
ClinPred		0.19	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.59
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs370375085; hg19: chr11-67059124; COSMIC: COSV57750930; COSMIC: COSV57750930;