NM_018288.4:c.1451C>T

Variant names:

• chr6-169704049-G-A
• rs1377997060
• NM_018288.4:c.1451C>T

Variant summary

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

The NM_018288.4(PHF10):​c.1451C>T​(p.Thr484Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000315 in 1,588,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T484A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: PHF10 NM_018288.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.33
• Publications: 0 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: 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=0.2096703).

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.1451C>T	p.Thr484Ile	missense	Exon 12 of 12	NP_060758.2	Q8WUB8-1
	C6orf120	NM_001029863.3	MANE Select	c.*1014G>A		3_prime_UTR	Exon 1 of 1	NP_001025034.1	Q7Z4R8
	PHF10	NM_133325.3		c.1445C>T	p.Thr482Ile	missense	Exon 12 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.1451C>T	p.Thr484Ile	missense	Exon 12 of 12	ENSP00000341805.4	Q8WUB8-1
	PHF10	ENST00000621772.4	TSL:1	c.1310C>T	p.Thr437Ile	missense	Exon 12 of 12	ENSP00000484117.1	Q8WUB8-3
	C6orf120	ENST00000332290.4	TSL:6 MANE Select	c.*1014G>A		3_prime_UTR	Exon 1 of 1	ENSP00000346931.1	Q7Z4R8

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000279 AC: 4 AN: 1435882 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 713952

African (AFR) AF: 0.00 AC: 0 AN: 31636

American (AMR) AF: 0.00 AC: 0 AN: 36328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25410

East Asian (EAS) AF: 0.00 AC: 0 AN: 38924

South Asian (SAS) AF: 0.00 AC: 0 AN: 80146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00000362 AC: 4 AN: 1105102

Other (OTH) AF: 0.00 AC: 0 AN: 59416

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

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

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

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

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

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	0.076
BayesDel_addAF	Benign	-0.0035	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.34
Sift	Benign	0.092	T
Sift4G	Uncertain	0.039	D
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.31		Loss of helix (P = 0.0104)
MVP		0.64
MPC		0.51
ClinPred		0.77	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.20
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1377997060; hg19: chr6-170104145;