Genetic Variant NM_018288.4:c.1327C>A (chr6-169705217-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018288.4(PHF10):c.1327C>A(p.His443Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,420 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. H443Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PHF10
NM_018288.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.41

Variant links:

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]

PHF10 links:

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]

C6orf120 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF10	NM_018288.4 link	c.1327C>A	p.His443Asn	missense_variant	Exon 11 of 12	ENST00000339209.9	NP_060758.2	Q8WUB8-1
C6orf120	NM_001029863.3 link	c.*2182G>T		3_prime_UTR_variant	Exon 1 of 1	ENST00000332290.4	NP_001025034.1	Q7Z4R8
PHF10	NM_133325.3 link	c.1321C>A	p.His441Asn	missense_variant	Exon 11 of 12		NP_579866.2	Q8WUB8-2
C6orf120	NM_001317342.2 link	c.*2182G>T		3_prime_UTR_variant	Exon 2 of 2		NP_001304271.1	Q7Z4R8B4DJ79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PHF10	ENST00000339209.9 link	c.1327C>A	p.His443Asn	missense_variant	Exon 11 of 12	1	NM_018288.4	ENSP00000341805.4	Q8WUB8-1
PHF10	ENST00000621772.4 link	c.1186C>A	p.His396Asn	missense_variant	Exon 11 of 12	1		ENSP00000484117.1	Q8WUB8-3
C6orf120	ENST00000332290.4 link	c.*2182G>T		3_prime_UTR_variant	Exon 1 of 1	6	NM_001029863.3	ENSP00000346931.1	Q7Z4R8
PHF10	ENST00000366780.8 link	c.1321C>A	p.His441Asn	missense_variant	Exon 11 of 12	5		ENSP00000355743.4	Q8WUB8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461420

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Uncertain

0.098

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.030

.;T;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.61

D;D;D

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

0.70

.;N;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.74

N;N;.

REVEL

Uncertain

0.37

Sift

Benign

0.64

T;T;.

Sift4G

Benign

0.30

T;T;T

Polyphen

1.0

D;B;.

Vest4

0.68

MutPred

0.45

.;Gain of sheet (P = 0.0043);.;

MVP

0.74

MPC

1.3

ClinPred

0.89

GERP RS

5.8

Varity_R

0.19

gMVP

0.50

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over