chr7-77901909-A-T

Variant names:

• chr7-77901909-A-T
• NM_001395272.1:c.332A>T

Variant summary

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

The NM_001395272.1(PHTF2):​c.332A>T​(p.Tyr111Phe) 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_001395272.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395272.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHTF2	NM_001395272.1	MANE Select	c.332A>T	p.Tyr111Phe	missense	Exon 6 of 19	NP_001382201.1	Q8N3S3-2
	PHTF2	NM_001366089.1		c.434A>T	p.Tyr145Phe	missense	Exon 6 of 19	NP_001353018.1	Q8N3S3-1
	PHTF2	NM_001127357.2		c.332A>T	p.Tyr111Phe	missense	Exon 5 of 18	NP_001120829.1	Q8N3S3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHTF2	ENST00000422959.8	TSL:5 MANE Select	c.332A>T	p.Tyr111Phe	missense	Exon 6 of 19	ENSP00000403042.2	Q8N3S3-2
	PHTF2	ENST00000248550.7	TSL:1	c.434A>T	p.Tyr145Phe	missense	Exon 6 of 19	ENSP00000248550.7	Q8N3S3-1
	PHTF2	ENST00000307305.12	TSL:1	c.320A>T	p.Tyr107Phe	missense	Exon 5 of 18	ENSP00000307699.8	Q8N3S3-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		8.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.52
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.44		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
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

hg19: chr7-77531226;