Variant chr16-67146295-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025187.5(PHAF1):c.1127A>C(p.Asn376Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000895 in 1,614,058 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00093 ( 1 hom. )

Consequence

PHAF1
NM_025187.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.51

Variant links:

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]

PHAF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02827382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHAF1	NM_025187.5 linkuse as main transcript	c.1127A>C	p.Asn376Thr	missense_variant	15/16	ENST00000219139.8	NP_079463.2	Q9BSU1-1A0A024R6W4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PHAF1	ENST00000219139.8 linkuse as main transcript	c.1127A>C	p.Asn376Thr	missense_variant	15/16	1	NM_025187.5	ENSP00000219139.3	Q9BSU1-1
PHAF1	ENST00000569600.5 linkuse as main transcript	c.1127A>C	p.Asn376Thr	missense_variant	16/17	1		ENSP00000455182.1	Q9BSU1-1
PHAF1	ENST00000569277.1 linkuse as main transcript	c.11A>C	p.Asn4Thr	missense_variant	1/3	3		ENSP00000464242.1	J3QRI8

Frequencies

GnomAD3 genomes

AF:

0.000592

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000720

AC:

181

AN:

251490

Hom.:

AF XY:

0.000736

AC XY:

100

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000926

AC:

1354

AN:

1461810

Hom.:

Cov.:

AF XY:

0.000894

AC XY:

650

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.00165

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00109

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.000591

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000952

Hom.:

Bravo

AF:

0.000612

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000692

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.000889

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0044

T;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.12

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

.;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.54

N;N

PROVEAN

Benign

1.4

N;N

REVEL

Benign

0.16

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.015

B;B

Vest4

0.60

MVP

0.18

MPC

0.36

ClinPred

0.048

GERP RS

5.4

Varity_R

0.16

gMVP

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over