14-18967667-T-C

Position:

• chr14-18967667-T-C

Variant summary

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

The NM_001145442.1(POTEM):​c.182T>C​(p.Met61Thr) 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. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 25)
• Consequence: POTEM NM_001145442.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0480

Genes affected

POTEM (HGNC:37096): (POTE ankyrin domain family member M) Predicted to be integral component of 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=0.18071076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POTEM	NM_001145442.1	c.182T>C	p.Met61Thr	missense_variant	1/11	ENST00000547889.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POTEM	ENST00000547889.6	c.182T>C	p.Met61Thr	missense_variant	1/11	1	NM_001145442.1	P1
POTEM	ENST00000616847.1	c.182T>C	p.Met61Thr	missense_variant, NMD_transcript_variant	1/12	1
POTEM	ENST00000552966.5	c.182T>C	p.Met61Thr	missense_variant, NMD_transcript_variant	1/12	2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 25

Bravo AF: 0.00000378

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 05, 2023

The c.182T>C (p.M61T) alteration is located in exon 1 (coding exon 1) of the POTEM gene. This alteration results from a T to C substitution at nucleotide position 182, causing the methionine (M) at amino acid position 61 to be replaced by a threonine (T). 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	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.85
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.4	N
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.28	T
Vest4		0.45
MutPred		0.35		Gain of catalytic residue at C65 (P = 0.0107);
MVP		0.040
ClinPred		0.21	T
Varity_R		0.21
gMVP		0.086

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: rs1307737665; hg19: chr14-19553598;