chr1-70300788-T-G

Position:

• chr1-70300788-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030816.5(ANKRD13C):​c.897A>C​(p.Lys299Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD13C NM_030816.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83

Genes affected

ANKRD13C (HGNC:25374): (ankyrin repeat domain 13C) Enables signaling receptor binding activity. Involved in protein retention in ER lumen; regulation of anoikis; and regulation of signaling receptor activity. Located in perinuclear region of cytoplasm. Colocalizes with endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD13C (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36722043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD13C	NM_030816.5	c.897A>C	p.Lys299Asn	missense_variant	7/13	ENST00000370944.9	NP_110443.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD13C	ENST00000370944.9	c.897A>C	p.Lys299Asn	missense_variant	7/13	1	NM_030816.5	ENSP00000359982.4
ANKRD13C	ENST00000262346.6	c.792A>C	p.Lys264Asn	missense_variant	6/12	1		ENSP00000262346.6
ANKRD13C	ENST00000490846.5	n.234A>C		non_coding_transcript_exon_variant	3/5	5

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2024

The c.897A>C (p.K299N) alteration is located in exon 7 (coding exon 7) of the ANKRD13C gene. This alteration results from a A to C substitution at nucleotide position 897, causing the lysine (K) at amino acid position 299 to be replaced by an asparagine (N). 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	0.47
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	0.0033
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.14
Sift	Benign	0.050	D;D
Sift4G	Uncertain	0.033	D;D
Polyphen		0.015	B;B
Vest4		0.61
MutPred		0.43		Loss of ubiquitination at K299 (P = 0.011);.;
MVP		0.67
MPC		0.79
ClinPred		0.94	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.76

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-70766471;