chr7-77840260-C-T

Variant names:

• chr7-77840260-C-T
• rs1795766643
• NM_001395272.1:c.5C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001395272.1(PHTF2):​c.5C>T​(p.Ala2Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000688 in 1,454,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: PHTF2 NM_001395272.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.07
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36904305).

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.5C>T	p.Ala2Val	missense	Exon 2 of 19	NP_001382201.1	Q8N3S3-2
	PHTF2	NM_001366089.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 19	NP_001353018.1	Q8N3S3-1
	PHTF2	NM_001127357.2		c.5C>T	p.Ala2Val	missense	Exon 1 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.5C>T	p.Ala2Val	missense	Exon 2 of 19	ENSP00000403042.2	Q8N3S3-2
	PHTF2	ENST00000248550.7	TSL:1	c.5C>T	p.Ala2Val	missense	Exon 1 of 19	ENSP00000248550.7	Q8N3S3-1
	PHTF2	ENST00000307305.12	TSL:1	c.5C>T	p.Ala2Val	missense	Exon 2 of 18	ENSP00000307699.8	Q8N3S3-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000688 AC: 10 AN: 1454214 Hom.: 0 Cov.: 27 AF XY: 0.00000414 AC XY: 3 AN XY: 723848

African (AFR) AF: 0.00 AC: 0 AN: 33292

American (AMR) AF: 0.00 AC: 0 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.00 AC: 0 AN: 85984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000905 AC: 10 AN: 1105492

Other (OTH) AF: 0.00 AC: 0 AN: 60088

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.50
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.0	N
PhyloP100		6.1
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.18
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.033	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.24		Gain of MoRF binding (P = 0.0985)
MVP		0.24
MPC		0.46
ClinPred		0.75	D
GERP RS		3.9
PromoterAI		-0.078	Neutral
Varity_R		0.12
gMVP		0.57
Mutation Taster		=79/21	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: rs1795766643; hg19: chr7-77469577; COSMIC: COSV50326845;