7-121362539-T-C

Position:

• chr7-121362539-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.382+358A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,930 control chromosomes in the GnomAD database, including 5,864 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 (5864 hom., cov: 32)
• Consequence: FAM3C NM_014888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.89).
• 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	Protein	UniProt
FAM3C	NM_014888.3	c.382+358A>G		intron_variant		ENST00000359943.8	NP_055703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM3C	ENST00000359943.8	c.382+358A>G		intron_variant		1	NM_014888.3	ENSP00000353025.3
FAM3C	ENST00000412653.5	c.382+358A>G		intron_variant		4		ENSP00000408636.1
FAM3C	ENST00000426156.1	c.292+358A>G		intron_variant		5		ENSP00000414940.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38573 AN: 151812 Hom.: 5847 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0406

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.254 AC: 38630 AN: 151930 Hom.: 5864 Cov.: 32 AF XY: 0.249 AC XY: 18530 AN XY: 74270

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0405

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.229

Alfa AF: 0.158 Hom.: 439

Bravo AF: 0.259

Asia WGS AF: 0.136 AC: 472 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.80

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: rs2536165; hg19: chr7-121002593;