chr3-56628560-T-C

Position:

• chr3-56628560-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365635.2(TASOR):​c.3802A>G​(p.Arg1268Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TASOR NM_001365635.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75

Genes affected

TASOR (HGNC:30314): (transcription activation suppressor) Enables chromatin binding activity. Involved in negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; protein localization to heterochromatin; and regulation of gene expression. Located in heterochromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11936316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TASOR	NM_001365635.2	c.3802A>G	p.Arg1268Gly	missense_variant	19/24	ENST00000683822.1	NP_001352564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TASOR	ENST00000683822.1	c.3802A>G	p.Arg1268Gly	missense_variant	19/24		NM_001365635.2	ENSP00000508241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1447894 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 720424

Gnomad4 AFR exome AF: 0.0000302

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: 0.0000167

GnomAD4 genome Cov.: 32

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

Jul 27, 2024

The c.3802A>G (p.R1268G) alteration is located in exon 19 (coding exon 19) of the FAM208A gene. This alteration results from a A to G substitution at nucleotide position 3802, causing the arginine (R) at amino acid position 1268 to be replaced by a glycine (G). 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
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	.;.;.;T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.052
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.5	N;N;N;.
REVEL	Benign	0.061
Sift	Benign	0.11	T;T;.;.
Sift4G	Benign	0.29	T;T;T;T
Polyphen		0.035	B;B;B;.
Vest4		0.40
MutPred		0.28		.;Gain of glycosylation at S1270 (P = 0.0239);.;.;
MVP		0.068
MPC		0.36
ClinPred		0.77	D
GERP RS		4.3
gMVP		0.16

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: chr3-56662588;