rs4286788

Variant names:

• chr6-169705629-T-C
• rs4286788
• NM_018288.4:c.1209A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_018288.4(PHF10):​c.1209A>G​(p.Gln403Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00082 in 1,467,854 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00042 (3 hom.)
• Consequence: PHF10 NM_018288.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0430
• Publications: 3 publications found

Genes affected

PHF10 (HGNC:18250): (PHD finger protein 10) This gene contains a predicted ORF that encodes a protein with two zinc finger domains. The function of the encoded protein is not known. Sequence analysis suggests that multiple alternatively spliced transcript variants are derived from this gene but the full-length nature of only two of them is known. These two splice variants encode different isoforms. A pseudogene for this gene is located on Xq28. [provided by RefSeq, Jul 2008]

C6orf120 (HGNC:21247): (chromosome 6 open reading frame 120) This gene encodes a conserved, N-glycosylated protein that likely functions in the cellular response to endoplasmic reticulum stress. This protein is able to induce apoptosis in vitro in CD4+ T-cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 6-169705629-T-C is Benign according to our data. Variant chr6-169705629-T-C is described in ClinVar as Benign. ClinVar VariationId is 712642.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.043 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018288.4. 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
	PHF10	NM_018288.4	MANE Select	c.1209A>G	p.Gln403Gln	synonymous	Exon 10 of 12	NP_060758.2	Q8WUB8-1
	C6orf120	NM_001029863.3	MANE Select	c.*2594T>C		3_prime_UTR	Exon 1 of 1	NP_001025034.1	Q7Z4R8
	PHF10	NM_133325.3		c.1203A>G	p.Gln401Gln	synonymous	Exon 10 of 12	NP_579866.2	Q8WUB8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHF10	ENST00000339209.9	TSL:1 MANE Select	c.1209A>G	p.Gln403Gln	synonymous	Exon 10 of 12	ENSP00000341805.4	Q8WUB8-1
	PHF10	ENST00000621772.4	TSL:1	c.1068A>G	p.Gln356Gln	synonymous	Exon 10 of 12	ENSP00000484117.1	Q8WUB8-3
	C6orf120	ENST00000332290.4	TSL:6 MANE Select	c.*2594T>C		3_prime_UTR	Exon 1 of 1	ENSP00000346931.1	Q7Z4R8

Frequencies

GnomAD3 genomes AF: 0.00429 AC: 653 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

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: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00104 AC: 260 AN: 250680 AF XY: 0.000686

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000420 AC: 552 AN: 1315544 Hom.: 3 Cov.: 20 AF XY: 0.000319 AC XY: 211 AN XY: 662364

African (AFR) AF: 0.0154 AC: 472 AN: 30562

American (AMR) AF: 0.000741 AC: 33 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25198

East Asian (EAS) AF: 0.00 AC: 0 AN: 38984

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.000192 AC: 1 AN: 5198

European-Non Finnish (NFE) AF: 0.00000306 AC: 3 AN: 979010

Other (OTH) AF: 0.000758 AC: 42 AN: 55434

GnomAD4 genome AF: 0.00428 AC: 652 AN: 152310 Hom.: 0 Cov.: 33 AF XY: 0.00432 AC XY: 322 AN XY: 74472

African (AFR) AF: 0.0152 AC: 633 AN: 41578

American (AMR) AF: 0.000981 AC: 15 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00160 Hom.: 3

Bravo AF: 0.00503

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.1
DANN	Benign	0.83
PhyloP100		0.043
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs4286788; hg19: chr6-170105725;