Genetic Variant NM_173611.4:c.209C>A (chr15-38464169-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_173611.4(FAM98B):c.209C>A(p.Thr70Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,459,832 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. T70M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

FAM98B
NM_173611.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.58

Variant links:

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]

FAM98B links:

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ACMG classification

Classification made for transcript

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=0.32591832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM98B	NM_173611.4 link	c.209C>A	p.Thr70Lys	missense_variant	Exon 2 of 8	ENST00000397609.6	NP_775882.2	Q52LJ0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAM98B	ENST00000397609.6 link	c.209C>A	p.Thr70Lys	missense_variant	Exon 2 of 8	5	NM_173611.4	ENSP00000380734.2	Q52LJ0-2
FAM98B	ENST00000491535.5 link	c.209C>A	p.Thr70Lys	missense_variant	Exon 2 of 7	1		ENSP00000453166.1	Q52LJ0-1
FAM98B	ENST00000305752.4 link	n.21C>A		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249974

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135112

show subpopulations

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:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1459832

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726134

show subpopulations

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:

0.0000583

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

.;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.15

Sift

Benign

0.20

T;T

Sift4G

Benign

0.89

T;T

Polyphen

0.99

.;D

Vest4

0.45

MutPred

0.50

Gain of ubiquitination at T70 (P = 0.0101);Gain of ubiquitination at T70 (P = 0.0101);

MVP

0.54

MPC

0.56

ClinPred

0.82

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over