Genetic Variant NM_001040443.3:c.35T>C (chr13-49496036-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001040443.3(PHF11):c.35T>C(p.Val12Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. V12E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

PHF11
NM_001040443.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

1 publications found

Variant links:

Genes affected

PHF11 (HGNC:17024): (PHD finger protein 11) This gene encodes a protein containing a PHD (plant homeodomain) type zinc finger. This gene has been identified in some studies as a candidate gene for asthma. Naturally-occurring readthrough transcription may occur from the upstream SETDB2 (SET domain bifurcated 2) gene to this locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

PHF11 links:

SETDB2-PHF11 (HGNC:):

SETDB2-PHF11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055113077).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040443.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHF11	NM_001040443.3	MANE Select	c.35T>C	p.Val12Ala	missense	Exon 1 of 10	NP_001035533.1	Q9UIL8-1
PHF11	NM_001040444.3		c.-245T>C		5_prime_UTR	Exon 1 of 11	NP_001035534.1	Q9UIL8-2
PHF11	NM_001419873.1		c.-598T>C		5_prime_UTR	Exon 1 of 11	NP_001406802.1	Q9UIL8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHF11	ENST00000378319.8	TSL:1 MANE Select	c.35T>C	p.Val12Ala	missense	Exon 1 of 10	ENSP00000367570.3	Q9UIL8-1
PHF11	ENST00000941732.1		c.35T>C	p.Val12Ala	missense	Exon 1 of 10	ENSP00000611791.1
PHF11	ENST00000873990.1		c.35T>C	p.Val12Ala	missense	Exon 1 of 10	ENSP00000544049.1

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73858

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41170

American (AMR)

AF:

0.00

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67744

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.29

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.082

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.25

M_CAP

Benign

0.0098

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

-1.1

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.22

REVEL

Benign

0.066

Sift

Benign

0.38

Sift4G

Benign

0.22

Polyphen

0.0

Vest4

0.019

MutPred

0.20

Gain of loop (P = 0.0312)

MVP

0.19

MPC

0.30

ClinPred

0.055

GERP RS

-2.0

PromoterAI

-0.14

Neutral

(source)

Varity_R

0.020

gMVP

0.21

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over