Genetic Variant FAM3C:c.467+74_467+75dupAA (chr7-121359967-A-ATT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014888.3(FAM3C):c.467+74_467+75dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00368 in 749,544 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0040 ( 2 hom., cov: 0)

Exomes 𝑓: 0.0036 ( 0 hom. )

Consequence

FAM3C
NM_014888.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.455

Publications

2 publications found

Variant links:

Genes affected

FAM3C (HGNC:18664): (FAM3 metabolism regulating signaling molecule C) This gene is a member of the family with sequence similarity 3 (FAM3) family and encodes a secreted protein with a GG domain. A change in expression of this protein has been noted in pancreatic cancer-derived cells. [provided by RefSeq, Mar 2010]

FAM3C links:

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ACMG classification

Classification was made for transcript

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

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM3C	NM_014888.3 link	c.467+74_467+75dupAA		intron_variant	Intron 8 of 9	ENST00000359943.8	NP_055703.1	Q92520

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAM3C	ENST00000359943.8 link	c.467+75_467+76insAA	intron_variant	Intron 8 of 9	1	NM_014888.3	ENSP00000353025.3	Q92520
FAM3C	ENST00000850865.1 link	c.467+75_467+76insAA	intron_variant	Intron 8 of 9			ENSP00000520951.1
FAM3C	ENST00000412653.5 link	c.88_89insAA	downstream_gene_variant		4		ENSP00000408636.1	C9JMN4
FAM3C	ENST00000426156.1 link	c.124_125insAA	downstream_gene_variant		5		ENSP00000414940.1	C9JP35

Frequencies

GnomAD3 genomes

AF:

0.00405

AC:

610

AN:

150738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000793

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.000195

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000429

Gnomad OTH

AF:

0.00194

GnomAD4 exome

AF:

0.00360

AC:

2153

AN:

598698

Hom.:

AF XY:

0.00341

AC XY:

1101

AN XY:

322980

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0260

AC:

294

AN:

11314

American (AMR)

AF:

0.00247

AC:

AN:

31634

Ashkenazi Jewish (ASJ)

AF:

0.00294

AC:

AN:

18352

East Asian (EAS)

AF:

0.000356

AC:

AN:

33736

South Asian (SAS)

AF:

0.00213

AC:

123

AN:

57666

European-Finnish (FIN)

AF:

0.00208

AC:

AN:

42840

Middle Eastern (MID)

AF:

0.00355

AC:

AN:

2814

European-Non Finnish (NFE)

AF:

0.00369

AC:

1365

AN:

370288

Other (OTH)

AF:

0.00426

AC:

128

AN:

30054

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.277

Heterozygous variant carriers

275

549

824

1098

1373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<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:

0.00403

AC:

608

AN:

150846

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

285

AN XY:

73660

show subpopulations

African (AFR)

AF:

0.0137

AC:

561

AN:

41094

American (AMR)

AF:

0.000726

AC:

AN:

15154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.000209

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.000195

AC:

AN:

10274

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000429

AC:

AN:

67626

Other (OTH)

AF:

0.00192

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00

Hom.:

863

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.46

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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7-121359967-AT-ATTT

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