rs2536163

chr7-121362856-C-T

Variant summary

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

The NM_014888.3(FAM3C):c.382+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,124,474 control chromosomes in the GnomAD database, including 25,614 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 0.25 (5872 hom., cov: 32)
  • Exomes 𝑓: 0.19 (19742 hom.)
• Consequence: FAM3C NM_014888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM3C	NM_014888.3	c.382+41G>A		intron_variant		ENST00000359943.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM3C	ENST00000359943.8	c.382+41G>A		intron_variant		1	NM_014888.3	P1
FAM3C	ENST00000412653.5	c.382+41G>A		intron_variant		4
FAM3C	ENST00000426156.1	c.292+41G>A		intron_variant		5
FAM3C	ENST00000497622.1	n.515G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38632 AN: 151920 Hom.: 5855 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0406

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.232

GnomAD3 exomes AF: 0.192 AC: 45212 AN: 235748 Hom.: 5031 AF XY: 0.189 AC XY: 24129 AN XY: 127806

Gnomad AFR exome AF: 0.425

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.0450

Gnomad SAS exome AF: 0.200

Gnomad FIN exome AF: 0.184

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.179

GnomAD4 exome AF: 0.192 AC: 186465 AN: 972436 Hom.: 19742 Cov.: 13 AF XY: 0.192 AC XY: 96732 AN XY: 504560

Gnomad4 AFR exome AF: 0.429

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.0285

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.254 AC: 38689 AN: 152038 Hom.: 5872 Cov.: 32 AF XY: 0.250 AC XY: 18564 AN XY: 74318

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0405

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.230

Alfa AF: 0.227 Hom.: 1073

Bravo AF: 0.259

Asia WGS AF: 0.139 AC: 480 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	16
Dann	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2536163; hg19: chr7-121002910; COSMIC: COSV63435131;