7-121378525-C-T

Variant names:

• chr7-121378525-C-T
• rs917727
• NM_014888.3:c.118+385G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014888.3(FAM3C):​c.118+385G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,882 control chromosomes in the GnomAD database, including 8,821 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 0.32 (8821 hom., cov: 31)
• Consequence: FAM3C NM_014888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 24 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM3C	NM_014888.3	c.118+385G>A		intron_variant	Intron 3 of 9	ENST00000359943.8	NP_055703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM3C	ENST00000359943.8	c.118+385G>A		intron_variant	Intron 3 of 9	1	NM_014888.3	ENSP00000353025.3
FAM3C	ENST00000850865.1	c.118+385G>A		intron_variant	Intron 3 of 9			ENSP00000520951.1
FAM3C	ENST00000412653.5	c.118+385G>A		intron_variant	Intron 3 of 7	4		ENSP00000408636.1
FAM3C	ENST00000426156.1	c.28+385G>A		intron_variant	Intron 4 of 8	5		ENSP00000414940.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48723 AN: 151764 Hom.: 8804 Cov.: 31

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.321 AC: 48782 AN: 151882 Hom.: 8821 Cov.: 31 AF XY: 0.313 AC XY: 23211 AN XY: 74214

African (AFR) AF: 0.495 AC: 20468 AN: 41378

American (AMR) AF: 0.267 AC: 4082 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1084 AN: 3470

East Asian (EAS) AF: 0.125 AC: 646 AN: 5170

South Asian (SAS) AF: 0.214 AC: 1027 AN: 4808

European-Finnish (FIN) AF: 0.220 AC: 2309 AN: 10518

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18220 AN: 67952

Other (OTH) AF: 0.321 AC: 678 AN: 2114

Alfa AF: 0.279 Hom.: 18122

Bravo AF: 0.336

Asia WGS AF: 0.232 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.70
PhyloP100		-0.0020
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: rs917727; hg19: chr7-121018579;