1-70354120-C-T

Variant names:

• chr1-70354120-C-T
• NM_030816.5:c.289G>A

Variant summary

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

The NM_030816.5(ANKRD13C):​c.289G>A​(p.Gly97Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ANKRD13C NM_030816.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.71
• Publications: 0 publications found

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]

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=0.10989019).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030816.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD13C	NM_030816.5	MANE Select	c.289G>A	p.Gly97Ser	missense	Exon 1 of 13	NP_110443.3	Q8N6S4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD13C	ENST00000370944.9	TSL:1 MANE Select	c.289G>A	p.Gly97Ser	missense	Exon 1 of 13	ENSP00000359982.4	Q8N6S4-1
	ANKRD13C	ENST00000262346.6	TSL:1	c.289G>A	p.Gly97Ser	missense	Exon 1 of 12	ENSP00000262346.6	Q8N6S4-2
	ANKRD13C	ENST00000888140.1		c.289G>A	p.Gly97Ser	missense	Exon 1 of 14	ENSP00000558200.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461308 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726892

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111632

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.7
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.013
Sift	Benign	0.18	T
Sift4G	Benign	0.91	T
Polyphen		0.041	B
Vest4		0.10
MutPred		0.29		Gain of glycosylation at G97 (P = 0.0034)
MVP		0.44
MPC		0.62
ClinPred		0.39	T
GERP RS		2.8
Varity_R		0.078
gMVP		0.23
Mutation Taster		=84/16	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: chr1-70819803;