rs10953356

Positions:

• chr7-77820281-A-G
• chr7-77820281-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000422959.8(PHTF2):​c.-35-19940A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,088 control chromosomes in the GnomAD database, including 4,364 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4364 hom., cov: 32)
• Consequence: PHTF2 ENST00000422959.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHTF2	NM_001395272.1	c.-35-19940A>G		intron_variant		ENST00000422959.8
PHTF2	XM_011516422.4	c.-35-19940A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHTF2	ENST00000422959.8	c.-35-19940A>G		intron_variant		5	NM_001395272.1	A1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34952 AN: 151970 Hom.: 4361 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.230 AC: 34965 AN: 152088 Hom.: 4364 Cov.: 32 AF XY: 0.228 AC XY: 16960 AN XY: 74336

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.238

Alfa AF: 0.250 Hom.: 5164

Bravo AF: 0.223

Asia WGS AF: 0.220 AC: 768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.7
DANN	Benign	0.61

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: rs10953356; hg19: chr7-77449598;