rs1372177914

Variant names:

• chr6-169704017-T-G
• rs1372177914
• NM_018288.4:c.1483A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018288.4(PHF10):​c.1483A>C​(p.Ser495Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,254 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 (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 33)
• Consequence: PHF10 NM_018288.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28822368).

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.1483A>C	p.Ser495Arg	missense	Exon 12 of 12	NP_060758.2	Q8WUB8-1
	C6orf120	NM_001029863.3	MANE Select	c.*982T>G		3_prime_UTR	Exon 1 of 1	NP_001025034.1	Q7Z4R8
	PHF10	NM_133325.3		c.1477A>C	p.Ser493Arg	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.1483A>C	p.Ser495Arg	missense	Exon 12 of 12	ENSP00000341805.4	Q8WUB8-1
	PHF10	ENST00000621772.4	TSL:1	c.1342A>C	p.Ser448Arg	missense	Exon 12 of 12	ENSP00000484117.1	Q8WUB8-3
	C6orf120	ENST00000332290.4	TSL:6 MANE Select	c.*982T>G		3_prime_UTR	Exon 1 of 1	ENSP00000346931.1	Q7Z4R8

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152254 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152254 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74396

African (AFR) AF: 0.0000482 AC: 2 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 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	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.023
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.69	N
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.085	T
Polyphen		0.010	B
Vest4		0.59
MutPred		0.33		Gain of solvent accessibility (P = 0.0023)
MVP		0.62
MPC		0.84
ClinPred		0.93	D
GERP RS		6.1
Varity_R		0.42
gMVP		0.40
Mutation Taster		=73/27	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: rs1372177914; hg19: chr6-170104113;