17-6445118-C-T

Position:

• chr17-6445118-C-T

Variant summary

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

The NM_019013.3(PIMREG):​c.8C>T​(p.Ser3Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,234 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PIMREG NM_019013.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31

Genes affected

PIMREG (HGNC:25483): (PICALM interacting mitotic regulator) Predicted to be involved in cell division. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC107985017 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
PIMREG	NM_019013.3	c.8C>T	p.Ser3Phe	missense_variant	2/6	ENST00000572447.6	NP_061886.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIMREG	ENST00000572447.6	c.8C>T	p.Ser3Phe	missense_variant	2/6	1	NM_019013.3	ENSP00000459235.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441234 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 715610

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: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.8C>T (p.S3F) alteration is located in exon 2 (coding exon 1) of the FAM64A gene. This alteration results from a C to T substitution at nucleotide position 8, causing the serine (S) at amino acid position 3 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.0076	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	.;T;T;T;T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.81	.;T;.;T;T;T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.56	D;D;D;D;D;D
MetaSVM	Benign	-0.75	T
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.9	.;D;.;.;.;.
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	.;D;.;.;.;.
Sift4G	Uncertain	0.0070	D;D;D;D;D;D
Polyphen		0.98	D;D;.;.;.;D
Vest4		0.66
MutPred		0.53		Loss of phosphorylation at S3 (P = 0.0421);Loss of phosphorylation at S3 (P = 0.0421);Loss of phosphorylation at S3 (P = 0.0421);Loss of phosphorylation at S3 (P = 0.0421);Loss of phosphorylation at S3 (P = 0.0421);Loss of phosphorylation at S3 (P = 0.0421);
MVP		0.68
MPC		0.62
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.48
gMVP		0.25

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: chr17-6348438;