rs752380468

Variant names:

• chr1-6620242-C-G
• NM_153812.3:c.581C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-6620242-C-G
• chr1-6620242-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153812.3(PHF13):​c.581C>G​(p.Thr194Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. T194I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PHF13 NM_153812.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

Genes affected

PHF13 (HGNC:22983): (PHD finger protein 13) Enables chromatin binding activity. Involved in mitotic chromosome condensation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047312528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF13	NM_153812.3	c.581C>G	p.Thr194Ser	missense_variant	Exon 3 of 4	ENST00000377648.5	NP_722519.2
PHF13	XM_011540762.2	c.608C>G	p.Thr203Ser	missense_variant	Exon 3 of 4		XP_011539064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF13	ENST00000377648.5	c.581C>G	p.Thr194Ser	missense_variant	Exon 3 of 4	1	NM_153812.3	ENSP00000366876.4
PHF13	ENST00000495385.1	n.345-1950C>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461740 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727148

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.23
Eigen_PC	Benign	0.012
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.093
Sift	Benign	0.79	T
Sift4G	Benign	0.96	T
Polyphen		0.036	B
Vest4		0.13
MutPred		0.11		Gain of ubiquitination at K197 (P = 0.0962);
MVP		0.12
MPC		0.24
ClinPred		0.29	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.070
gMVP		0.13

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.

Other links and lift over

hg19: chr1-6680302;