15-38481394-C-G

Variant names:

• chr15-38481394-C-G
• NM_173611.4:c.832C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173611.4(FAM98B):​c.832C>G​(p.Leu278Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)
• Consequence: FAM98B NM_173611.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.547

Genes affected

FAM98B (HGNC:26773): (family with sequence similarity 98 member B) Enables identical protein binding activity and protein methyltransferase activity. Involved in positive regulation of cell population proliferation; positive regulation of gene expression; and protein methylation. Located in cytoplasm and nucleoplasm. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3873704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM98B	NM_173611.4	c.832C>G	p.Leu278Val	missense_variant	Exon 7 of 8	ENST00000397609.6	NP_775882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM98B	ENST00000397609.6	c.832C>G	p.Leu278Val	missense_variant	Exon 7 of 8	5	NM_173611.4	ENSP00000380734.2
FAM98B	ENST00000491535.5	c.832C>G	p.Leu278Val	missense_variant	Exon 7 of 7	1		ENSP00000453166.1
FAM98B	ENST00000559431.1	c.259-3198C>G		intron_variant	Intron 3 of 3	5		ENSP00000453926.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.832C>G (p.L278V) alteration is located in exon 7 (coding exon 7) of the FAM98B gene. This alteration results from a C to G substitution at nucleotide position 832, causing the leucine (L) at amino acid position 278 to be replaced by a valine (V). 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	Benign	0.12
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	.;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.21
Sift	Benign	0.088	T;T
Sift4G	Uncertain	0.053	T;T
Polyphen		0.97	.;D
Vest4		0.31
MutPred		0.74		Gain of MoRF binding (P = 0.0858);Gain of MoRF binding (P = 0.0858);
MVP		0.54
MPC		0.35
ClinPred		0.91	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.099
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr15-38773595;