21-13610485-A-T

Position:

• chr21-13610485-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174981.6(POTED):​c.257A>T​(p.His86Leu) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 5)
• Consequence: POTED NM_174981.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.80

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07889885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POTED	NM_174981.6	c.257A>T	p.His86Leu	missense_variant	1/11	ENST00000299443.6
POTED	XM_006723997.4	c.257A>T	p.His86Leu	missense_variant	1/8
POTED	XM_011529550.3	c.257A>T	p.His86Leu	missense_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POTED	ENST00000299443.6	c.257A>T	p.His86Leu	missense_variant	1/11	1	NM_174981.6	P1
POTED	ENST00000620442.4	c.257A>T	p.His86Leu	missense_variant	1/8	1

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 5

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

May 04, 2022

The c.257A>T (p.H86L) alteration is located in exon 1 (coding exon 1) of the POTED gene. This alteration results from a A to T substitution at nucleotide position 257, causing the histidine (H) at amino acid position 86 to be replaced by a leucine (L). 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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.69
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.55	T
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.46	.;P
Vest4		0.14
MutPred		0.30		Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);
MVP		0.043
ClinPred		0.17	T
Varity_R		0.078
gMVP		0.015

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: chr21-14982806;