16-67147456-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_025187.5(PHAF1):c.*325G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00506 in 313,300 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0053 (5 hom.)
• Consequence: PHAF1 NM_025187.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.20

Genes affected

PHAF1 (HGNC:29564): (phagosome assembly factor 1) Predicted to be involved in Golgi to plasma membrane protein transport. Located in phagophore assembly site. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 16-67147456-G-A is Benign according to our data. Variant chr16-67147456-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2646609.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHAF1	NM_025187.5	c.*325G>A		3_prime_UTR_variant	16/16	ENST00000219139.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHAF1	ENST00000219139.8	c.*325G>A		3_prime_UTR_variant	16/16	1	NM_025187.5	P1
PHAF1	ENST00000569277.1	c.270G>A	p.Gly90=	synonymous_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.00480 AC: 730 AN: 152206 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0201

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00592

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00329 AC: 64 AN: 19450 Hom.: 1 AF XY: 0.00392 AC XY: 38 AN XY: 9690

Gnomad AFR exome AF: 0.000513

Gnomad AMR exome AF: 0.00211

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0221

Gnomad NFE exome AF: 0.00431

Gnomad OTH exome AF: 0.00386

GnomAD4 exome AF: 0.00532 AC: 856 AN: 160976 Hom.: 5 Cov.: 0 AF XY: 0.00509 AC XY: 415 AN XY: 81486

Gnomad4 AFR exome AF: 0.000726

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.000490

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0217

Gnomad4 NFE exome AF: 0.00540

Gnomad4 OTH exome AF: 0.00514

GnomAD4 genome AF: 0.00479 AC: 730 AN: 152324 Hom.: 9 Cov.: 32 AF XY: 0.00509 AC XY: 379 AN XY: 74484

Gnomad4 AFR AF: 0.000938

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0201

Gnomad4 NFE AF: 0.00592

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00531 Hom.: 0

Bravo AF: 0.00326

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

PHAF1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	13
Dann	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149463851; hg19: chr16-67181359;