7-124858962-G-C

Position:

• chr7-124858962-G-C

Variant summary

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

The NM_015450.3(POT1):​c.697C>G​(p.Leu233Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,356 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: POT1 NM_015450.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.12

Genes affected

POT1 (HGNC:17284): (protection of telomeres 1) This gene is a member of the telombin family and encodes a nuclear protein involved in telomere maintenance. Specifically, this protein functions as a member of a multi-protein complex that binds to the TTAGGG repeats of telomeres, regulating telomere length and protecting chromosome ends from illegitimate recombination, catastrophic chromosome instability, and abnormal chromosome segregation. Increased transcriptional expression of this gene is associated with stomach carcinogenesis and its progression. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POT1	NM_015450.3	c.697C>G	p.Leu233Val	missense_variant	9/19	ENST00000357628.8	NP_056265.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POT1	ENST00000357628.8	c.697C>G	p.Leu233Val	missense_variant	9/19	2	NM_015450.3	ENSP00000350249	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449356 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 720736

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;D;D
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D;D;.
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.7	M;.;.
MutationTaster	Benign	0.95	D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.6	N;N;.
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D;D;.
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		0.70	P;.;.
Vest4		0.63
MutPred		0.61		Loss of stability (P = 0.0196);.;.;
MVP		0.59
MPC		1.9
ClinPred		0.91	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.50
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr7-124499016;