dbSNP rs369190079: FAM98C:p.Ala103Ala (chr19-38403654-G-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_174905.4(FAM98C):c.309G>T(p.Ala103Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,408,518 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 5 hom. )

Consequence

FAM98C
NM_174905.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.393

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 19-38403654-G-T is Benign according to our data. Variant chr19-38403654-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3033480.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.393 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174905.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM98C	NM_174905.4	MANE Select	c.309G>T	p.Ala103Ala	synonymous	Exon 3 of 8	NP_777565.3
	FAM98C	NM_001351675.1		c.309G>T	p.Ala103Ala	synonymous	Exon 3 of 6	NP_001338604.1	Q17RN3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM98C	ENST00000252530.10	TSL:1 MANE Select	c.309G>T	p.Ala103Ala	synonymous	Exon 3 of 8	ENSP00000252530.4	Q17RN3-1
FAM98C	ENST00000343358.11	TSL:1	c.309G>T	p.Ala103Ala	synonymous	Exon 3 of 6	ENSP00000340348.6	Q17RN3-2
FAM98C	ENST00000588262.5	TSL:1	c.309G>T	p.Ala103Ala	synonymous	Exon 3 of 5	ENSP00000467974.1	K7EQT7

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

193

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00240

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00119

AC:

AN:

29438

AF XY:

0.00129

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000259

Gnomad ASJ exome

AF:

0.000735

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00200

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00251

AC:

3157

AN:

1256180

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

1516

AN XY:

612448

show subpopulations

African (AFR)

AF:

0.000281

AC:

AN:

24936

American (AMR)

AF:

0.000775

AC:

AN:

14194

Ashkenazi Jewish (ASJ)

AF:

0.000321

AC:

AN:

18716

East Asian (EAS)

AF:

0.0000356

AC:

AN:

28052

South Asian (SAS)

AF:

0.00175

AC:

106

AN:

60702

European-Finnish (FIN)

AF:

0.000161

AC:

AN:

31034

Middle Eastern (MID)

AF:

0.000506

AC:

AN:

3950

European-Non Finnish (NFE)

AF:

0.00287

AC:

2936

AN:

1022712

Other (OTH)

AF:

0.00160

AC:

AN:

51884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

209

419

628

838

1047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00127

AC:

193

AN:

152338

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41584

American (AMR)

AF:

0.000588

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00124

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00240

AC:

163

AN:

68032

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000690

Hom.:

Bravo

AF:

0.00148

Asia WGS

AF:

0.000867

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

FAM98C-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.5

(source)

DANN

Benign

0.80

PhyloP100

0.39

PromoterAI

0.033

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over