rs2254595

Variant names:

• chr7-121367195-T-C
• rs2254595
• NM_014888.3:c.273-3007A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FAM3C	NM_014888.3	c.273-3007A>G		intron_variant	Intron 5 of 9	ENST00000359943.8	NP_055703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM3C	ENST00000359943.8	c.273-3007A>G		intron_variant	Intron 5 of 9	1	NM_014888.3	ENSP00000353025.3
FAM3C	ENST00000850865.1	c.273-3007A>G		intron_variant	Intron 5 of 9			ENSP00000520951.1
FAM3C	ENST00000412653.5	c.273-3007A>G		intron_variant	Intron 5 of 7	4		ENSP00000408636.1
FAM3C	ENST00000426156.1	c.183-3007A>G		intron_variant	Intron 6 of 8	5		ENSP00000414940.1

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

African (AFR) AF: 0.817 AC: 33898 AN: 41478

American (AMR) AF: 0.433 AC: 6606 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1627 AN: 3466

East Asian (EAS) AF: 0.165 AC: 857 AN: 5182

South Asian (SAS) AF: 0.424 AC: 2040 AN: 4812

European-Finnish (FIN) AF: 0.414 AC: 4367 AN: 10560

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32209 AN: 67922

Other (OTH) AF: 0.520 AC: 1100 AN: 2114

Alfa AF: 0.494 Hom.: 10148

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
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2254595; hg19: chr7-121007249;