Variant 19-38403462-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_174905.4(FAM98C):c.190G>A(p.Ala64Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 1,405,082 control chromosomes in the GnomAD database, including 853 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 121 hom., cov: 32)

Exomes 𝑓: 0.022 ( 732 hom. )

Consequence

FAM98C
NM_174905.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.722

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011990964).

BP6

Variant 19-38403462-G-A is Benign according to our data. Variant chr19-38403462-G-A is described in ClinVar as [Benign]. Clinvar id is 3059360.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FAM98C	NM_174905.4 linkuse as main transcript	c.190G>A	p.Ala64Thr	missense_variant	2/8	ENST00000252530.10
FAM98C	NM_001351675.1 linkuse as main transcript	c.190G>A	p.Ala64Thr	missense_variant	2/6
FAM98C	XM_017026354.2 linkuse as main transcript	c.190G>A	p.Ala64Thr	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM98C	ENST00000252530.10 linkuse as main transcript	c.190G>A	p.Ala64Thr	missense_variant	2/8	1	NM_174905.4	P1	Q17RN3-1

Frequencies

GnomAD3 genomes

AF:

0.0245

AC:

3722

AN:

152190

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00629

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0830

Gnomad ASJ

AF:

0.0302

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.0105

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0175

Gnomad OTH

AF:

0.0325

GnomAD3 exomes

AF:

0.0492

AC:

860

AN:

17476

Hom.:

AF XY:

0.0426

AC XY:

452

AN XY:

10620

show subpopulations

Gnomad AFR exome

AF:

0.00488

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.0358

Gnomad EAS exome

AF:

0.157

Gnomad SAS exome

AF:

0.0154

Gnomad FIN exome

AF:

0.0227

Gnomad NFE exome

AF:

0.0214

Gnomad OTH exome

AF:

0.0394

GnomAD4 exome

AF:

0.0224

AC:

28109

AN:

1252784

Hom.:

732

Cov.:

AF XY:

0.0222

AC XY:

13546

AN XY:

611412

show subpopulations

Gnomad4 AFR exome

AF:

0.00473

Gnomad4 AMR exome

AF:

0.114

Gnomad4 ASJ exome

AF:

0.0260

Gnomad4 EAS exome

AF:

0.163

Gnomad4 SAS exome

AF:

0.00992

Gnomad4 FIN exome

AF:

0.0146

Gnomad4 NFE exome

AF:

0.0187

Gnomad4 OTH exome

AF:

0.0252

GnomAD4 genome

AF:

0.0244

AC:

3723

AN:

152298

Hom.:

121

Cov.:

AF XY:

0.0259

AC XY:

1925

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00630

Gnomad4 AMR

AF:

0.0830

Gnomad4 ASJ

AF:

0.0302

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.0146

Gnomad4 NFE

AF:

0.0175

Gnomad4 OTH

AF:

0.0326

Alfa

AF:

0.0182

Hom.:

Bravo

AF:

0.0302

TwinsUK

AF:

0.0205

AC:

ALSPAC

AF:

0.0156

AC:

ESP6500AA

AF:

0.00464

AC:

ESP6500EA

AF:

0.0147

AC:

ExAC

AF:

0.0146

AC:

1069

Asia WGS

AF:

0.0590

AC:

203

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

FAM98C-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.0065

T;T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.66

T;T;T

MetaRNN

Benign

0.0012

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.73

Sift4G

Benign

0.83

T;T;T

Polyphen

0.0060, 0.025

.;B;B

Vest4

0.12

MPC

1.2

ClinPred

0.0022

GERP RS

2.0

Varity_R

0.034

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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