15-38465367-C-T

Variant names:

• chr15-38465367-C-T
• rs777802537
• NM_173611.4:c.316C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_173611.4(FAM98B):​c.316C>T​(p.Arg106Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,601,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: FAM98B NM_173611.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.07
• Publications: 6 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.813

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173611.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM98B	NM_173611.4	MANE Select	c.316C>T	p.Arg106Cys	missense	Exon 3 of 8	NP_775882.2	Q52LJ0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM98B	ENST00000397609.6	TSL:5 MANE Select	c.316C>T	p.Arg106Cys	missense	Exon 3 of 8	ENSP00000380734.2	Q52LJ0-2
	FAM98B	ENST00000491535.5	TSL:1	c.316C>T	p.Arg106Cys	missense	Exon 3 of 7	ENSP00000453166.1	Q52LJ0-1
	FAM98B	ENST00000559431.1	TSL:5	c.22C>T	p.Arg8Cys	missense	Exon 1 of 4	ENSP00000453926.1	H0YNA1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 151956 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000492 AC: 12 AN: 243698 AF XY: 0.0000455

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000717

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.000115 AC: 166 AN: 1449376 Hom.: 0 Cov.: 30 AF XY: 0.000125 AC XY: 90 AN XY: 720632

African (AFR) AF: 0.0000607 AC: 2 AN: 32940

American (AMR) AF: 0.00 AC: 0 AN: 42634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25784

East Asian (EAS) AF: 0.00 AC: 0 AN: 39304

South Asian (SAS) AF: 0.0000723 AC: 6 AN: 82950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.000129 AC: 143 AN: 1107156

Other (OTH) AF: 0.000251 AC: 15 AN: 59840

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 151956 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74224

African (AFR) AF: 0.00 AC: 0 AN: 41358

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000823 Hom.: 0

Bravo AF: 0.0000491

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		3.1
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.72		Gain of catalytic residue at L107 (P = 0.0107)
MVP		0.72
MPC		0.65
ClinPred		0.81	D
GERP RS		4.8
PromoterAI		0.019	Neutral
Varity_R		0.34
gMVP		0.65
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs777802537; hg19: chr15-38757568; COSMIC: COSV59843401;