NM_001136213.1:c.446G>T

Variant names:

• chr22-15690523-G-T
• rs772295021
• NM_001136213.1:c.446G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136213.1(POTEH):​c.446G>T​(p.Ser149Ile) 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. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S149N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 26)
• Consequence: POTEH NM_001136213.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.78
• Publications: 0 publications found

Genes affected

POTEH (HGNC:133): (POTE ankyrin domain family member H) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11647761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POTEH	NM_001136213.1	c.446G>T	p.Ser149Ile	missense_variant	Exon 1 of 11	ENST00000343518.11	NP_001129685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POTEH	ENST00000343518.11	c.446G>T	p.Ser149Ile	missense_variant	Exon 1 of 11	5	NM_001136213.1	ENSP00000340610.6
POTEH	ENST00000452800.1	n.278G>T		non_coding_transcript_exon_variant	Exon 1 of 12	5		ENSP00000442107.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-3.8
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.9	N;.
Sift	Uncertain	0.0090	D;.
Sift4G	Benign	0.087	T;T
Vest4		0.14
MutPred		0.34		.;Gain of catalytic residue at K116 (P = 0);
MVP		0.014
ClinPred		0.15	T
GERP RS		-1.1
PromoterAI		0.0038	Neutral
gMVP		0.62
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs772295021; hg19: chr14-19553751;