NM_207354.3:c.23T>G

Variant names:

• chr11-67289483-T-G
• NM_207354.3:c.23T>G

Variant summary

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

The NM_207354.3(ANKRD13D):​c.23T>G​(p.Phe8Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD13D NM_207354.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.346
• 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.23T>G	p.Phe8Cys	missense_variant	Exon 1 of 15	ENST00000511455.7	NP_997237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD13D	ENST00000511455.7	c.23T>G	p.Phe8Cys	missense_variant	Exon 1 of 15	1	NM_207354.3	ENSP00000427130.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.23T>G (p.F8C) alteration is located in exon 1 (coding exon 1) of the ANKRD13D gene. This alteration results from a T to G substitution at nucleotide position 23, causing the phenylalanine (F) at amino acid position 8 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
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	26
DANN	Uncertain	0.99
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.95	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.94	T
PhyloP100		0.35
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.43
MutPred		0.71		Gain of disorder (P = 0.0665);
MVP		0.13
MPC		1.3
ClinPred		0.91	D
GERP RS		2.3
PromoterAI		-0.25	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.88
Mutation Taster		=82/18	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: chr11-67056954;