rs771267278

Variant names:

• chr8-132825369-A-T
• rs771267278
• NM_016018.5:c.1742A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-132825369-A-T
• chr8-132825369-A-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016018.5(PHF20L1):​c.1742A>T​(p.His581Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000635 in 1,496,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: PHF20L1 NM_016018.5 missense, splice_region
• Scores: Splicing: ADA: 0.008614
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29
• Publications: 0 publications found

Genes affected

PHF20L1 (HGNC:24280): (PHD finger protein 20 like 1) Predicted to enable metal ion binding activity. Predicted to be involved in histone acetylation and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of NSL complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.087302655).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016018.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF20L1	NM_016018.5	MANE Select	c.1742A>T	p.His581Leu	missense splice_region	Exon 14 of 21	NP_057102.4
	PHF20L1	NM_001438309.1		c.1757A>T	p.His586Leu	missense splice_region	Exon 14 of 21	NP_001425238.1
	PHF20L1	NM_001438310.1		c.1754A>T	p.His585Leu	missense splice_region	Exon 14 of 21	NP_001425239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF20L1	ENST00000395386.7	TSL:5 MANE Select	c.1742A>T	p.His581Leu	missense splice_region	Exon 14 of 21	ENSP00000378784.2	A8MW92-1
	PHF20L1	ENST00000939789.1		c.1757A>T	p.His586Leu	missense splice_region	Exon 14 of 21	ENSP00000609848.1
	PHF20L1	ENST00000905699.1		c.1754A>T	p.His585Leu	missense splice_region	Exon 14 of 21	ENSP00000575758.1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152044 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000635 AC: 8 AN: 125886 AF XY: 0.0000878

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000163

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000617 AC: 83 AN: 1344156 Hom.: 0 Cov.: 23 AF XY: 0.0000631 AC XY: 42 AN XY: 665250

African (AFR) AF: 0.00 AC: 0 AN: 28688

American (AMR) AF: 0.00 AC: 0 AN: 28178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23354

East Asian (EAS) AF: 0.00 AC: 0 AN: 35570

South Asian (SAS) AF: 0.00 AC: 0 AN: 74474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47390

Middle Eastern (MID) AF: 0.000189 AC: 1 AN: 5294

European-Non Finnish (NFE) AF: 0.0000775 AC: 81 AN: 1045648

Other (OTH) AF: 0.0000180 AC: 1 AN: 55560

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152044 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74246

African (AFR) AF: 0.0000241 AC: 1 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000604

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000485 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.3
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.023
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.095	T
Polyphen		0.035	B
Vest4		0.34
MutPred		0.15		Gain of MoRF binding (P = 0.1094)
MVP		0.068
MPC		0.35
ClinPred		0.16	T
GERP RS		3.0
Varity_R		0.16
gMVP		0.37
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0086
dbscSNV1_RF	Benign	0.23
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

Other links and lift over

dbSNP: rs771267278; hg19: chr8-133837614;