rs2254595

chr7-121367195-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014888.3(FAM3C):c.273-3007A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,004 control chromosomes in the GnomAD database, including 25,122 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (25122 hom., cov: 32)
• Consequence: FAM3C NM_014888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM3C	NM_014888.3	c.273-3007A>G		intron_variant		ENST00000359943.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM3C	ENST00000359943.8	c.273-3007A>G		intron_variant		1	NM_014888.3	P1
FAM3C	ENST00000412653.5	c.273-3007A>G		intron_variant		4
FAM3C	ENST00000426156.1	c.183-3007A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83102 AN: 151886 Hom.: 25080 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.519

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.547 AC: 83198 AN: 152004 Hom.: 25122 Cov.: 32 AF XY: 0.536 AC XY: 39799 AN XY: 74306

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.520

Alfa AF: 0.493 Hom.: 9007

Bravo AF: 0.561

Asia WGS AF: 0.364 AC: 1262 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.38
Dann	Benign	0.39

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

LitVar

Other links and lift over

dbSNP: rs2254595; hg19: chr7-121007249;