Genetic Variant NM_016605.3:c.196A>C (chr5-138344884-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016605.3(FAM53C):c.196A>C(p.Asn66His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,611,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

FAM53C
NM_016605.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Publications

0 publications found

Variant links:

Genes affected

FAM53C (HGNC:1336): (family with sequence similarity 53 member C) The protein encoded by this gene belongs to the FAM53 protein family. FAM53 protein family members bind to a transcriptional regulator that modulates cell proliferation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

FAM53C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025883049).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016605.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM53C	NM_016605.3	MANE Select	c.196A>C	p.Asn66His	missense	Exon 4 of 5	NP_057689.1	Q9NYF3
FAM53C	NM_001135647.2		c.196A>C	p.Asn66His	missense	Exon 4 of 5	NP_001129119.1	Q9NYF3
FAM53C	NM_001350195.2		c.166A>C	p.Asn56His	missense	Exon 4 of 5	NP_001337124.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM53C	ENST00000239906.10	TSL:1 MANE Select	c.196A>C	p.Asn66His	missense	Exon 4 of 5	ENSP00000239906.5	Q9NYF3
FAM53C	ENST00000434981.6	TSL:1	c.196A>C	p.Asn66His	missense	Exon 4 of 5	ENSP00000403705.2	Q9NYF3
FAM53C	ENST00000513056.5	TSL:1	c.137-512A>C		intron	N/A	ENSP00000425154.1	D6RE00

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000844

AC:

AN:

248744

AF XY:

0.0000446

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000206

AC:

AN:

1459404

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

725996

show subpopulations

African (AFR)

AF:

0.000779

AC:

AN:

33384

American (AMR)

AF:

0.00

AC:

AN:

44196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25892

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

85942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110926

Other (OTH)

AF:

0.0000498

AC:

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000250

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.000893

AC:

AN:

41426

American (AMR)

AF:

0.0000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

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:

0.000237

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

Eigen

Benign

0.035

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.72

M_CAP

Benign

0.0082

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

1.4

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.84

REVEL

Benign

0.078

Sift

Benign

0.12

Sift4G

Benign

0.28

Polyphen

0.69

Vest4

0.47

MVP

0.30

MPC

0.33

ClinPred

0.039

GERP RS

5.3

Varity_R

0.044

gMVP

0.095

Mutation Taster

=90/10

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