Variant chr19-38405419-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_174905.4(FAM98C):c.631T>C(p.Trp211Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,614,128 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

FAM98C
NM_174905.4 missense, splice_region

Scores

Splicing: ADA: 0.3385

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.56

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026520133).

BP6

Variant 19-38405419-T-C is Benign according to our data. Variant chr19-38405419-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3034905.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FAM98C	NM_174905.4 linkuse as main transcript	c.631T>C	p.Trp211Arg	missense_variant, splice_region_variant	5/8	ENST00000252530.10
FAM98C	XM_017026354.2 linkuse as main transcript	c.*12T>C		splice_region_variant, 3_prime_UTR_variant	5/6
FAM98C	NM_001351675.1 linkuse as main transcript	c.556-100T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM98C	ENST00000252530.10 linkuse as main transcript	c.631T>C	p.Trp211Arg	missense_variant, splice_region_variant	5/8	1	NM_174905.4	P1	Q17RN3-1

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

299

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00690

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000473

AC:

118

AN:

249534

Hom.:

AF XY:

0.000251

AC XY:

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.00697

Gnomad AMR exome

AF:

0.000232

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:

0.000213

AC:

312

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

122

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00821

Gnomad4 AMR exome

AF:

0.000313

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:

0.00000540

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.00196

AC:

298

AN:

152280

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

137

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00686

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000411

Hom.:

Bravo

AF:

0.00202

ESP6500AA

AF:

0.00702

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000627

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

FAM98C-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 05, 2019

This variant is classified as likely 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

Pathogenic

0.83

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.60

M_CAP

Benign

0.039

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.49

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-11

REVEL

Uncertain

0.36

Sift

Uncertain

0.0030

Sift4G

Benign

0.095

Polyphen

1.0

Vest4

0.87

MutPred

0.76

Gain of helix (P = 0.0696);

MVP

0.84

MPC

1.0

ClinPred

0.13

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.57

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.34

dbscSNV1_RF

Benign

0.59

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