Variant chr19-38403667-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_174905.4(FAM98C):c.322G>A(p.Glu108Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 1,415,012 control chromosomes in the GnomAD database, including 807 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 0.034 ( 113 hom., cov: 32)

Exomes 𝑓: 0.032 ( 694 hom. )

Consequence

FAM98C
NM_174905.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00400

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=0.0019147396).

BP6

Variant 19-38403667-G-A is Benign according to our data. Variant chr19-38403667-G-A is described in ClinVar as [Benign]. Clinvar id is 3057083.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0343 (5228/152294) while in subpopulation AFR AF= 0.051 (2121/41574). AF 95% confidence interval is 0.0492. There are 113 homozygotes in gnomad4. There are 2533 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 113 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FAM98C	NM_174905.4 linkuse as main transcript	c.322G>A	p.Glu108Lys	missense_variant	3/8	ENST00000252530.10
FAM98C	NM_001351675.1 linkuse as main transcript	c.322G>A	p.Glu108Lys	missense_variant	3/6
FAM98C	XM_017026354.2 linkuse as main transcript	c.322G>A	p.Glu108Lys	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM98C	ENST00000252530.10 linkuse as main transcript	c.322G>A	p.Glu108Lys	missense_variant	3/8	1	NM_174905.4	P1	Q17RN3-1

Frequencies

GnomAD3 genomes

AF:

0.0343

AC:

5216

AN:

152182

Hom.:

113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0509

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0190

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0439

Gnomad FIN

AF:

0.0332

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0306

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0259

AC:

1126

AN:

43402

Hom.:

AF XY:

0.0271

AC XY:

691

AN XY:

25456

show subpopulations

Gnomad AFR exome

AF:

0.0468

Gnomad AMR exome

AF:

0.0109

Gnomad ASJ exome

AF:

0.0275

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0422

Gnomad FIN exome

AF:

0.0272

Gnomad NFE exome

AF:

0.0272

Gnomad OTH exome

AF:

0.0400

GnomAD4 exome

AF:

0.0322

AC:

40660

AN:

1262718

Hom.:

694

Cov.:

AF XY:

0.0325

AC XY:

20030

AN XY:

615852

show subpopulations

Gnomad4 AFR exome

AF:

0.0512

Gnomad4 AMR exome

AF:

0.0147

Gnomad4 ASJ exome

AF:

0.0315

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0459

Gnomad4 FIN exome

AF:

0.0338

Gnomad4 NFE exome

AF:

0.0322

Gnomad4 OTH exome

AF:

0.0298

GnomAD4 genome

AF:

0.0343

AC:

5228

AN:

152294

Hom.:

113

Cov.:

AF XY:

0.0340

AC XY:

2533

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0510

Gnomad4 AMR

AF:

0.0190

Gnomad4 ASJ

AF:

0.0288

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0441

Gnomad4 FIN

AF:

0.0332

Gnomad4 NFE

AF:

0.0306

Gnomad4 OTH

AF:

0.0242

Alfa

AF:

0.0279

Hom.:

Bravo

AF:

0.0335

ESP6500AA

AF:

0.0275

AC:

ESP6500EA

AF:

0.0190

AC:

135

ExAC

AF:

0.0187

AC:

2077

Asia WGS

AF:

0.0240

AC:

AN:

3476

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

Oct 28, 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

0.12

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.1

DANN

Benign

0.90

DEOGEN2

Benign

0.010

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.54

T;T;T

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.82

Sift4G

Benign

0.14

T;T;T

Polyphen

0.0060, 0.021

.;B;B

Vest4

0.10

MPC

1.3

ClinPred

0.00058

GERP RS

0.29

Varity_R

0.046

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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