chr21-13610458-C-T

Position:

• chr21-13610458-C-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.230C>T​(p.Thr77Met) 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: 4)
• Consequence: POTED NM_174981.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.487

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=0.07530993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POTED	NM_174981.6	c.230C>T	p.Thr77Met	missense_variant	1/11	ENST00000299443.6
POTED	XM_006723997.4	c.230C>T	p.Thr77Met	missense_variant	1/8
POTED	XM_011529550.3	c.230C>T	p.Thr77Met	missense_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POTED	ENST00000299443.6	c.230C>T	p.Thr77Met	missense_variant	1/11	1	NM_174981.6	P1
POTED	ENST00000620442.4	c.230C>T	p.Thr77Met	missense_variant	1/8	1

Frequencies

GnomAD3 genomes Cov.: 4

GnomAD4 exome Cov.: 26

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

Dec 13, 2021

The c.230C>T (p.T77M) alteration is located in exon 1 (coding exon 1) of the POTED gene. This alteration results from a C to T substitution at nucleotide position 230, causing the threonine (T) at amino acid position 77 to be replaced by a methionine (M). 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	0.097
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.93
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00042	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.52	T
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.99	.;D
Vest4		0.13
MutPred		0.16		Loss of catalytic residue at T77 (P = 0.0702);Loss of catalytic residue at T77 (P = 0.0702);
MVP		0.043
ClinPred		0.22	T
Varity_R		0.033
gMVP		0.013

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

LitVar

Other links and lift over

dbSNP: rs201981080; hg19: chr21-14982779;