7-77901909-A-T

Variant names:

• chr7-77901909-A-T
• ENST00000248550.7:c.434A>T

Variant summary

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

The NM_001366089.1(PHTF2):​c.434A>T​(p.Tyr145Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PHTF2 NM_001366089.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95

Genes affected

PHTF2 (HGNC:13411): (putative homeodomain transcription factor 2) Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
PHTF2	NM_001366089.1	c.434A>T	p.Tyr145Phe	missense_variant	Exon 6 of 19		NP_001353018.1
PHTF2	NM_001127357.2	c.332A>T	p.Tyr111Phe	missense_variant	Exon 5 of 18		NP_001120829.1
PHTF2	NM_001395272.1	c.332A>T	p.Tyr111Phe	missense_variant	Exon 6 of 19		NP_001382201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHTF2	ENST00000422959.8	c.332A>T	p.Tyr111Phe	missense_variant	Exon 6 of 19	5		ENSP00000403042.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.332A>T (p.Y111F) alteration is located in exon 5 (coding exon 5) of the PHTF2 gene. This alteration results from a A to T substitution at nucleotide position 332, causing the tyrosine (Y) at amino acid position 111 to be replaced by a phenylalanine (F). 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	0.51
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;.;.;.;.;.;.;T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;.
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.52	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Uncertain	2.4	M;.;.;.;.;.;.;M
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.5	.;D;D;D;D;D;D;D
REVEL	Uncertain	0.52
Sift	Pathogenic	0.0	.;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D
Polyphen		1.0	D;P;D;.;.;D;.;D
Vest4		0.61
MutPred		0.44		Gain of MoRF binding (P = 0.1705);.;.;.;.;.;.;Gain of MoRF binding (P = 0.1705);
MVP		0.31
MPC		0.52
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.40
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr7-77531226;