Variant 19-38403221-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_174905.4(FAM98C):c.65+3A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 1,558,560 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

FAM98C
NM_174905.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.9997

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00900

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 19-38403221-A-G is Benign according to our data. Variant chr19-38403221-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3040624.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
FAM98C	NM_174905.4 linkuse as main transcript	c.65+3A>G	splice_donor_region_variant, intron_variant	ENST00000252530.10
FAM98C	NM_001351675.1 linkuse as main transcript	c.65+3A>G	splice_donor_region_variant, intron_variant
FAM98C	XM_017026354.2 linkuse as main transcript	c.65+3A>G	splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM98C	ENST00000252530.10 linkuse as main transcript	c.65+3A>G		splice_donor_region_variant, intron_variant		1	NM_174905.4	P1	Q17RN3-1

Frequencies

GnomAD3 genomes

AF:

0.00176

AC:

268

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000392

AC:

AN:

183866

Hom.:

AF XY:

0.000340

AC XY:

AN XY:

103062

show subpopulations

Gnomad AFR exome

AF:

0.00606

Gnomad AMR exome

AF:

0.000553

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000122

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000114

Gnomad OTH exome

AF:

0.000236

GnomAD4 exome

AF:

0.000151

AC:

212

AN:

1406430

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

699264

show subpopulations

Gnomad4 AFR exome

AF:

0.00520

Gnomad4 AMR exome

AF:

0.000439

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000498

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000916

Gnomad4 OTH exome

AF:

0.000516

GnomAD4 genome

AF:

0.00177

AC:

269

AN:

152130

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00581

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000644

Hom.:

Bravo

AF:

0.00152

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

Oct 28, 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

BayesDel_noAF

Benign

-0.42

Cadd

Benign

Dann

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.85

SpliceAI score (max)

0.74

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.74

Position offset: -3

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