rs774995655

Variant names:

• chr7-77910381-C-A
• rs774995655
• NM_001395272.1:c.646C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-77910381-C-A
• chr7-77910381-C-T

Variant summary

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

The NM_001395272.1(PHTF2):​c.646C>A​(p.Leu216Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,460,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. L216F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: PHTF2 NM_001395272.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.50
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11723119).

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.646C>A	p.Leu216Ile	missense	Exon 8 of 19	NP_001382201.1	Q8N3S3-2
	PHTF2	NM_001366089.1		c.748C>A	p.Leu250Ile	missense	Exon 8 of 19	NP_001353018.1	Q8N3S3-1
	PHTF2	NM_001127357.2		c.646C>A	p.Leu216Ile	missense	Exon 7 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.646C>A	p.Leu216Ile	missense	Exon 8 of 19	ENSP00000403042.2	Q8N3S3-2
	PHTF2	ENST00000248550.7	TSL:1	c.748C>A	p.Leu250Ile	missense	Exon 8 of 19	ENSP00000248550.7	Q8N3S3-1
	PHTF2	ENST00000307305.12	TSL:1	c.634C>A	p.Leu212Ile	missense	Exon 7 of 18	ENSP00000307699.8	Q8N3S3-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1460810 Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 6 AN XY: 726616

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111538

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.00083	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	N
PhyloP100		4.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.058
Sift	Benign	0.43	T
Sift4G	Benign	0.53	T
Polyphen		0.0020	B
Vest4		0.16
MutPred		0.47		Gain of catalytic residue at L250 (P = 0.0373)
MVP		0.18
MPC		0.16
ClinPred		0.79	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.31
Mutation Taster		=90/10	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: rs774995655; hg19: chr7-77539698;