rs7776725

chr7-121393067-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.-42+3095A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,098 control chromosomes in the GnomAD database, including 6,082 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 0.28 (6082 hom., cov: 32)
• Consequence: FAM3C NM_014888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM3C	NM_014888.3	c.-42+3095A>G		intron_variant		ENST00000359943.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM3C	ENST00000359943.8	c.-42+3095A>G		intron_variant		1	NM_014888.3	P1
FAM3C	ENST00000412653.5	c.-42+3232A>G		intron_variant		4
FAM3C	ENST00000426156.1	c.-188+3095A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42342 AN: 151980 Hom.: 6076 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.279 AC: 42364 AN: 152098 Hom.: 6082 Cov.: 32 AF XY: 0.273 AC XY: 20297 AN XY: 74366

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.281

Alfa AF: 0.269 Hom.: 7210

Bravo AF: 0.284

Asia WGS AF: 0.220 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.4
Dann	Benign	0.64

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: rs7776725; hg19: chr7-121033121;