21-13610401-G-A

Position:

• chr21-13610401-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_174981.6(POTED):​c.173G>A​(p.Arg58Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 4)
• Consequence: POTED NM_174981.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.875

Genes affected

POTED (HGNC:23822): (POTE ankyrin domain family member D) Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06720072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POTED	NM_174981.6	c.173G>A	p.Arg58Lys	missense_variant	1/11	ENST00000299443.6
POTED	XM_006723997.4	c.173G>A	p.Arg58Lys	missense_variant	1/8
POTED	XM_011529550.3	c.173G>A	p.Arg58Lys	missense_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POTED	ENST00000299443.6	c.173G>A	p.Arg58Lys	missense_variant	1/11	1	NM_174981.6	P1
POTED	ENST00000620442.4	c.173G>A	p.Arg58Lys	missense_variant	1/8	1

Frequencies

GnomAD3 genomes Cov.: 4

GnomAD4 exome Cov.: 14

GnomAD4 genome Cov.: 4

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

Jul 06, 2021

The c.173G>A (p.R58K) alteration is located in exon 1 (coding exon 1) of the POTED gene. This alteration results from a G to A substitution at nucleotide position 173, causing the arginine (R) at amino acid position 58 to be replaced by a lysine (K). 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	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Uncertain	0.98
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.50	T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.14	.;B
Vest4		0.054
MutPred		0.25		Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);
MVP		0.082
ClinPred		0.13	T
Varity_R		0.31
gMVP		0.037

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: chr21-14982722;