11-67292119-A-C

Variant names:

• chr11-67292119-A-C
• NM_207354.3:c.670A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207354.3(ANKRD13D):​c.670A>C​(p.Ser224Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. S224T) has been classified 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: 4.97
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16580337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD13D	NM_207354.3	c.670A>C	p.Ser224Arg	missense_variant	Exon 6 of 15	ENST00000511455.7	NP_997237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD13D	ENST00000511455.7	c.670A>C	p.Ser224Arg	missense_variant	Exon 6 of 15	1	NM_207354.3	ENSP00000427130.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.670A>C (p.S224R) alteration is located in exon 6 (coding exon 6) of the ANKRD13D gene. This alteration results from a A to C substitution at nucleotide position 670, causing the serine (S) at amino acid position 224 to be replaced by an arginine (R). 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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T;.;T;T
Eigen	Benign	0.14
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	.;D;.;D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;L;L
PhyloP100		5.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.97	N;N;N;N
REVEL	Benign	0.070
Sift	Benign	0.59	T;T;T;T
Sift4G	Benign	0.50	T;T;T;T
Polyphen		0.42	B;P;B;B
Vest4		0.25
MutPred		0.25		Loss of glycosylation at S137 (P = 0.0332);.;Loss of glycosylation at S137 (P = 0.0332);Loss of glycosylation at S137 (P = 0.0332);
MVP		0.36
MPC		0.73
ClinPred		0.64	D
GERP RS		4.0
Varity_R		0.32
gMVP		0.65
Mutation Taster		=71/29	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: chr11-67059590;