rs774995655

Variant names:

• chr7-77910381-C-A
• rs774995655
• ENST00000248550.7:c.748C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366089.1(PHTF2):​c.748C>A​(p.Leu250Ile) 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. 13/20 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. L250F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: PHTF2 NM_001366089.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.50

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 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHTF2	NM_001366089.1	c.748C>A	p.Leu250Ile	missense_variant	Exon 8 of 19		NP_001353018.1
PHTF2	NM_001127357.2	c.646C>A	p.Leu216Ile	missense_variant	Exon 7 of 18		NP_001120829.1
PHTF2	NM_001395272.1	c.646C>A	p.Leu216Ile	missense_variant	Exon 8 of 19		NP_001382201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHTF2	ENST00000422959.8	c.646C>A	p.Leu216Ile	missense_variant	Exon 8 of 19	5		ENSP00000403042.2

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

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: 0.0000108

Gnomad4 OTH exome AF: 0.00

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 v4.3

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;.;.;.;.;.;.;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.86	D;D;D;D;D;D;D;.
M_CAP	Benign	0.00083	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	N;.;.;.;.;.;.;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.090	.;N;N;N;N;N;N;N
REVEL	Benign	0.058
Sift	Benign	0.43	.;T;T;T;T;T;T;T
Sift4G	Benign	0.53	T;T;T;T;T;T;T;T
Polyphen		0.0020	B;B;B;.;.;B;.;B
Vest4		0.16
MutPred		0.47		Gain of catalytic residue at L250 (P = 0.0373);.;.;.;.;.;.;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs774995655; hg19: chr7-77539698;