dbSNP rs150024474: FAM98C:p.Glu108Lys (chr19-38403667-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

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 no assertion criteria provided B:1

Conservation

PhyloP100: -0.00400

Publications

5 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 -13 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 VariationId is 3057083.Status of the report is no_assertion_criteria_provided, 0 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 113 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.322G>A	p.Glu108Lys	missense	Exon 3 of 8	NP_777565.3
	FAM98C	NM_001351675.1		c.322G>A	p.Glu108Lys	missense	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.322G>A	p.Glu108Lys	missense	Exon 3 of 8	ENSP00000252530.4	Q17RN3-1
FAM98C	ENST00000343358.11	TSL:1	c.322G>A	p.Glu108Lys	missense	Exon 3 of 6	ENSP00000340348.6	Q17RN3-2
FAM98C	ENST00000588262.5	TSL:1	c.322G>A	p.Glu108Lys	missense	Exon 3 of 5	ENSP00000467974.1	K7EQT7

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

GnomAD2 exomes

AF:

0.0259

AC:

1126

AN:

43402

AF XY:

0.0271

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 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

African (AFR)

AF:

0.0512

AC:

1292

AN:

25222

American (AMR)

AF:

0.0147

AC:

238

AN:

16136

Ashkenazi Jewish (ASJ)

AF:

0.0315

AC:

583

AN:

18526

East Asian (EAS)

AF:

0.00

AC:

AN:

28622

South Asian (SAS)

AF:

0.0459

AC:

2776

AN:

60536

European-Finnish (FIN)

AF:

0.0338

AC:

1057

AN:

31276

Middle Eastern (MID)

AF:

0.0313

AC:

120

AN:

3836

European-Non Finnish (NFE)

AF:

0.0322

AC:

33039

AN:

1026384

Other (OTH)

AF:

0.0298

AC:

1555

AN:

52180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

2443

4886

7328

9771

12214

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1346

2692

4038

5384

6730

<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:

0.0343

AC:

5228

AN:

152294

Hom.:

113

Cov.:

AF XY:

0.0340

AC XY:

2533

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0510

AC:

2121

AN:

41574

American (AMR)

AF:

0.0190

AC:

291

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0288

AC:

100

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5162

South Asian (SAS)

AF:

0.0441

AC:

213

AN:

4830

European-Finnish (FIN)

AF:

0.0332

AC:

353

AN:

10620

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0306

AC:

2081

AN:

68020

Other (OTH)

AF:

0.0242

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

265

530

794

1059

1324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0301

Hom.:

219

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

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

FAM98C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.1

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.010

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.71

PhyloP100

-0.0040

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.39

REVEL

Benign

0.0030

Sift

Benign

0.88

Sift4G

Benign

0.14

Polyphen

0.0060

Vest4

0.10

MPC

1.3

ClinPred

0.00058

GERP RS

0.29

PromoterAI

0.0081

Neutral

(source)

Varity_R

0.046

gMVP

0.21

Mutation Taster

=100/0

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

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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