dbSNP rs10515808: FAM200C:p.Ala523Ser (chr5-160393924-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022090.5(FAM200C):c.1567G>T(p.Ala523Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 1,613,608 control chromosomes in the GnomAD database, including 7,131 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.075 ( 521 hom., cov: 32)

Exomes 𝑓: 0.091 ( 6610 hom. )

Consequence

FAM200C
NM_022090.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.473

Publications

17 publications found

Variant links:

Genes affected

FAM200C (HGNC:30804): (family with sequence similarity 200 member C) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAM200C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00157395).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0998 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM200C	NM_022090.5 link	c.1567G>T	p.Ala523Ser	missense_variant	Exon 2 of 2	ENST00000408953.4	NP_071373.2	Q8IZ13
FAM200C	NM_001303251.2 link	c.1567G>T	p.Ala523Ser	missense_variant	Exon 3 of 3		NP_001290180.1	Q8IZ13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM200C	ENST00000408953.4 link	c.1567G>T	p.Ala523Ser	missense_variant	Exon 2 of 2	2	NM_022090.5	ENSP00000386184.3		Q8IZ13
FAM200C	ENST00000523213.1 link	c.1567G>T	p.Ala523Ser	missense_variant	Exon 3 of 3	1		ENSP00000428831.1		Q8IZ13

Frequencies

GnomAD3 genomes

AF:

0.0754

AC:

11467

AN:

152114

Hom.:

521

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0379

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.0667

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0660

Gnomad FIN

AF:

0.0859

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.0864

GnomAD2 exomes

AF:

0.0784

AC:

19511

AN:

248968

AF XY:

0.0815

show subpopulations

Gnomad AFR exome

AF:

0.0379

Gnomad AMR exome

AF:

0.0485

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.0896

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.0871

GnomAD4 exome

AF:

0.0915

AC:

133676

AN:

1461376

Hom.:

6610

Cov.:

AF XY:

0.0917

AC XY:

66632

AN XY:

727024

show subpopulations

African (AFR)

AF:

0.0364

AC:

1217

AN:

33474

American (AMR)

AF:

0.0537

AC:

2400

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

3028

AN:

26128

East Asian (EAS)

AF:

0.000378

AC:

AN:

39682

South Asian (SAS)

AF:

0.0762

AC:

6571

AN:

86244

European-Finnish (FIN)

AF:

0.0863

AC:

4612

AN:

53418

Middle Eastern (MID)

AF:

0.123

AC:

711

AN:

5768

European-Non Finnish (NFE)

AF:

0.0988

AC:

109852

AN:

1111556

Other (OTH)

AF:

0.0873

AC:

5270

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

6548

13095

19643

26190

32738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3954

7908

11862

15816

19770

<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:

0.0753

AC:

11469

AN:

152232

Hom.:

521

Cov.:

AF XY:

0.0743

AC XY:

5527

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0378

AC:

1571

AN:

41544

American (AMR)

AF:

0.0666

AC:

1018

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

364

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5190

South Asian (SAS)

AF:

0.0663

AC:

320

AN:

4830

European-Finnish (FIN)

AF:

0.0859

AC:

911

AN:

10608

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6921

AN:

67982

Other (OTH)

AF:

0.0851

AC:

180

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

541

1082

1623

2164

2705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<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:

0.0921

Hom.:

2121

Bravo

AF:

0.0734

TwinsUK

AF:

0.0990

AC:

367

ALSPAC

AF:

0.0952

AC:

367

ESP6500AA

AF:

0.0399

AC:

176

ESP6500EA

AF:

0.102

AC:

881

ExAC

AF:

0.0787

AC:

9552

Asia WGS

AF:

0.0360

AC:

126

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.4

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.0065

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.28

.;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.4

N;N

PhyloP100

0.47

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.0070

Sift

Benign

1.0

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.0

B;B

Vest4

0.044

MPC

0.039

ClinPred

0.0015

GERP RS

1.0

Varity_R

0.030

gMVP

0.052

Mutation Taster

=99/1

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over