NM_001323043.2:c.1973delT

Variant names:

• chr1-113700866-TA-T
• rs1168463464
• NM_001323043.2:c.1973delT

Variant summary

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

The NM_001323043.2(PHTF1):​c.1973delT​(p.Leu658TyrfsTer44) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,966 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PHTF1 NM_001323043.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.29
• Publications: 0 publications found

Genes affected

PHTF1 (HGNC:8939): (putative homeodomain transcription factor 1) Predicted to be located in cis-Golgi network and endoplasmic reticulum membrane. Predicted to be integral component of membrane. [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_001323043.2. 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
	PHTF1	NM_001323043.2	MANE Select	c.1973delT	p.Leu658TyrfsTer44	frameshift	Exon 16 of 19	NP_001309972.1	Q9UMS5-1
	PHTF1	NM_001323041.2		c.1973delT	p.Leu658TyrfsTer44	frameshift	Exon 16 of 19	NP_001309970.1	Q9UMS5-1
	PHTF1	NM_001323042.2		c.1973delT	p.Leu658TyrfsTer44	frameshift	Exon 16 of 19	NP_001309971.1	Q9UMS5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHTF1	ENST00000369604.6	TSL:5 MANE Select	c.1973delT	p.Leu658TyrfsTer44	frameshift	Exon 16 of 19	ENSP00000358617.1	Q9UMS5-1
	PHTF1	ENST00000393357.6	TSL:1	c.1973delT	p.Leu658TyrfsTer44	frameshift	Exon 15 of 18	ENSP00000377025.2	Q9UMS5-1
	PHTF1	ENST00000873091.1		c.1973delT	p.Leu658TyrfsTer44	frameshift	Exon 16 of 19	ENSP00000543150.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458966 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725858

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33218

American (AMR) AF: 0.0000458 AC: 2 AN: 43686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 85716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111152

Other (OTH) AF: 0.00 AC: 0 AN: 60284

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0482410), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3
Mutation Taster		=29/171	disease causing (fs/PTC)

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: rs1168463464; hg19: chr1-114243488; COSMIC: COSV63366904; COSMIC: COSV63366904;