Variant chr19-38404991-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_174905.4(FAM98C):c.433G>A(p.Glu145Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

FAM98C
NM_174905.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.833

Variant links:

Genes affected

FAM98C (HGNC:27119): (family with sequence similarity 98 member C) Predicted to be part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

FAM98C links:

FAM98C (HGNC:):

FAM98C links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.065493464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM98C	NM_174905.4 linkuse as main transcript	c.433G>A	p.Glu145Lys	missense_variant	4/8	ENST00000252530.10	NP_777565.3	Q17RN3-1
FAM98C	NM_001351675.1 linkuse as main transcript	c.433G>A	p.Glu145Lys	missense_variant	4/6		NP_001338604.1
FAM98C	XM_017026354.2 linkuse as main transcript	c.433G>A	p.Glu145Lys	missense_variant	4/6		XP_016881843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM98C	ENST00000252530.10 linkuse as main transcript	c.433G>A	p.Glu145Lys	missense_variant	4/8	1	NM_174905.4	ENSP00000252530.4		Q17RN3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249390

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135408

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727244

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.433G>A (p.E145K) alteration is located in exon 4 (coding exon 4) of the FAM98C gene. This alteration results from a G to A substitution at nucleotide position 433, causing the glutamic acid (E) at amino acid position 145 to be replaced by a lysine (K). 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

0.073

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0019

T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.065

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.85

L;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.063

Sift

Benign

0.32

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.018

B;B

Vest4

0.095

MutPred

0.56

Gain of ubiquitination at E145 (P = 0.0037);Gain of ubiquitination at E145 (P = 0.0037);

MVP

0.31

MPC

0.23

ClinPred

0.055

GERP RS

1.1

Varity_R

0.045

gMVP

0.31

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over