15-38465275-A-G

Variant names:

• chr15-38465275-A-G
• rs771093185
• NM_173611.4:c.224A>G

Variant summary

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

The NM_173611.4(FAM98B):​c.224A>G​(p.Asp75Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,452,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D75V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM98B NM_173611.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21109879).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM98B	NM_173611.4	c.224A>G	p.Asp75Gly	missense_variant	Exon 3 of 8	ENST00000397609.6	NP_775882.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM98B	ENST00000397609.6	c.224A>G	p.Asp75Gly	missense_variant	Exon 3 of 8	5	NM_173611.4	ENSP00000380734.2
FAM98B	ENST00000491535.5	c.224A>G	p.Asp75Gly	missense_variant	Exon 3 of 7	1		ENSP00000453166.1
FAM98B	ENST00000305752.4	n.36A>G		non_coding_transcript_exon_variant	Exon 2 of 3	5
FAM98B	ENST00000559431.1	c.-71A>G		upstream_gene_variant		5		ENSP00000453926.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000821 AC: 2 AN: 243626 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 132014

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000688

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452914 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722756

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: 0.0000238

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.090
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.11
Sift	Benign	0.047	D;D
Sift4G	Benign	0.083	T;T
Polyphen		0.63	.;P
Vest4		0.26
MutPred		0.41		Gain of methylation at R74 (P = 0.0314);Gain of methylation at R74 (P = 0.0314);
MVP		0.68
MPC		0.57
ClinPred		0.78	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.33

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

LitVar

Other links and lift over

dbSNP: rs771093185; hg19: chr15-38757476;