chr13-49518114-G-T

Variant names:

• chr13-49518114-G-T
• rs765683187
• NM_001040443.3:c.421G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001040443.3(PHF11):​c.421G>T​(p.Ala141Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,620 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PHF11 NM_001040443.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25

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]

SETDB2-PHF11 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF11	NM_001040443.3	c.421G>T	p.Ala141Ser	missense_variant	Exon 4 of 10	ENST00000378319.8	NP_001035533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF11	ENST00000378319.8	c.421G>T	p.Ala141Ser	missense_variant	Exon 4 of 10	1	NM_001040443.3	ENSP00000367570.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249576 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134960

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455620 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 724490

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000508 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.39	T;.;T;.;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.75	T;T;T;.;T;T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.43	T;T;T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.0	M;.;.;.;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.3	N;.;D;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.030	D;.;D;T;D;T
Sift4G	Uncertain	0.016	D;D;D;D;D;D
Polyphen		1.0	D;D;.;.;.;.
Vest4		0.37
MutPred		0.64		Gain of disorder (P = 0.0441);Gain of disorder (P = 0.0441);.;.;.;.;
MVP		0.79
MPC		0.78
ClinPred		0.36	T
GERP RS		3.2
Varity_R		0.057
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.20		Position offset: 37

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

Publications

LitVar

Other links and lift over

dbSNP: rs765683187; hg19: chr13-50092250;