NM_016018.5:c.774A>G

Variant names:

• chr8-132804667-A-G
• rs148199331
• NM_016018.5:c.774A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_016018.5(PHF20L1):​c.774A>G​(p.Thr258Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000606 in 1,609,820 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (1 hom.)
• Consequence: PHF20L1 NM_016018.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.446
• Publications: 1 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 8-132804667-A-G is Benign according to our data. Variant chr8-132804667-A-G is described in ClinVar as Benign. ClinVar VariationId is 789772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.446 with no splicing effect.

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.774A>G	p.Thr258Thr	synonymous	Exon 8 of 21	NP_057102.4
	PHF20L1	NM_001438309.1		c.789A>G	p.Thr263Thr	synonymous	Exon 8 of 21	NP_001425238.1
	PHF20L1	NM_001438310.1		c.786A>G	p.Thr262Thr	synonymous	Exon 8 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.774A>G	p.Thr258Thr	synonymous	Exon 8 of 21	ENSP00000378784.2	A8MW92-1
	PHF20L1	ENST00000337920.8	TSL:1	c.696A>G	p.Thr232Thr	synonymous	Exon 7 of 8	ENSP00000338269.4	A8MW92-2
	PHF20L1	ENST00000315808.14	TSL:1	n.1057A>G		non_coding_transcript_exon	Exon 8 of 14

Frequencies

GnomAD3 genomes AF: 0.00273 AC: 415 AN: 151892 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00932

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00132

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: 0.0000884

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000803 AC: 201 AN: 250176 AF XY: 0.000628

Gnomad AFR exome AF: 0.00927

Gnomad AMR exome AF: 0.000929

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000382 AC: 557 AN: 1457810 Hom.: 1 Cov.: 28 AF XY: 0.000332 AC XY: 241 AN XY: 725310

African (AFR) AF: 0.00914 AC: 304 AN: 33254

American (AMR) AF: 0.000918 AC: 41 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.000523 AC: 3 AN: 5740

European-Non Finnish (NFE) AF: 0.000153 AC: 170 AN: 1108910

Other (OTH) AF: 0.000631 AC: 38 AN: 60182

GnomAD4 genome AF: 0.00275 AC: 418 AN: 152010 Hom.: 1 Cov.: 32 AF XY: 0.00245 AC XY: 182 AN XY: 74298

African (AFR) AF: 0.00937 AC: 389 AN: 41530

American (AMR) AF: 0.00132 AC: 20 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000884 AC: 6 AN: 67886

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00141 Hom.: 1

Bravo AF: 0.00314

EpiCase AF: 0.000219

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.0
DANN	Uncertain	0.98
PhyloP100		-0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs148199331; hg19: chr8-133816912;