rs34227712

Variant names:

• chr6-169710265-C-A
• rs34227712
• NM_018288.4:c.1084G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-169710265-C-A
• chr6-169710265-C-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.1084G>T​(p.Val362Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V362I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PHF10 NM_018288.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.90
• 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]

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=0.16918227).

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.1084G>T	p.Val362Leu	missense	Exon 9 of 12	NP_060758.2	Q8WUB8-1
	PHF10	NM_133325.3		c.1078G>T	p.Val360Leu	missense	Exon 9 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.1084G>T	p.Val362Leu	missense	Exon 9 of 12	ENSP00000341805.4	Q8WUB8-1
	PHF10	ENST00000621772.4	TSL:1	c.943G>T	p.Val315Leu	missense	Exon 9 of 12	ENSP00000484117.1	Q8WUB8-3
	PHF10	ENST00000612128.1	TSL:1	c.1084G>T	p.Val362Leu	missense	Exon 9 of 9	ENSP00000479515.1	S5FZ81

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460372 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726490

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4954

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111576

Other (OTH) AF: 0.00 AC: 0 AN: 60260

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.061
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.60	N
REVEL	Uncertain	0.34
Sift	Benign	0.64	T
Sift4G	Benign	0.76	T
Polyphen		0.0090	B
Vest4		0.24
MutPred		0.33		Gain of helix (P = 0.0117)
MVP		0.64
MPC		0.47
ClinPred		0.78	D
GERP RS		5.9
Varity_R		0.069
gMVP		0.20
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs34227712; hg19: chr6-170110361;