14-18967637-A-T

Position:

• chr14-18967637-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001145442.1(POTEM):​c.152A>T​(p.Asp51Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D51E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 4)
  • Exomes 𝑓: 0.0000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POTEM NM_001145442.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14205202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POTEM	NM_001145442.1	c.152A>T	p.Asp51Val	missense_variant	1/11	ENST00000547889.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POTEM	ENST00000547889.6	c.152A>T	p.Asp51Val	missense_variant	1/11	1	NM_001145442.1	P1
POTEM	ENST00000616847.1	c.152A>T	p.Asp51Val	missense_variant, NMD_transcript_variant	1/12	1
POTEM	ENST00000552966.5	c.152A>T	p.Asp51Val	missense_variant, NMD_transcript_variant	1/12	2

Frequencies

GnomAD3 genomes Cov.: 4

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000165 AC: 1 AN: 606238 Hom.: 0 Cov.: 12 AF XY: 0.00000316 AC XY: 1 AN XY: 316386

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000296

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 4

ExAC AF: 0.0000167 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.1	N
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.31
MutPred		0.36		Gain of catalytic residue at S46 (P = 0);
MVP		0.12
ClinPred		0.60	D
Varity_R		0.11
gMVP		0.022

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: rs781609693; hg19: chr14-19553568;