rs12706341

Variant names:

• chr7-121384654-G-A
• rs12706341
• NM_014888.3:c.-41-1644C>T

Variant summary

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

The NM_014888.3(FAM3C):​c.-41-1644C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,122 control chromosomes in the GnomAD database, including 2,172 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 0.16 (2172 hom., cov: 32)
• Consequence: FAM3C NM_014888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM3C	NM_014888.3	c.-41-1644C>T		intron_variant	Intron 1 of 9	ENST00000359943.8	NP_055703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM3C	ENST00000359943.8	c.-41-1644C>T		intron_variant	Intron 1 of 9	1	NM_014888.3	ENSP00000353025.3
FAM3C	ENST00000850865.1	c.-41-1644C>T		intron_variant	Intron 1 of 9			ENSP00000520951.1
FAM3C	ENST00000412653.5	c.-41-1644C>T		intron_variant	Intron 1 of 7	4		ENSP00000408636.1
FAM3C	ENST00000426156.1	c.-187-1644C>T		intron_variant	Intron 1 of 8	5		ENSP00000414940.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25034 AN: 152004 Hom.: 2169 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.165 AC: 25057 AN: 152122 Hom.: 2172 Cov.: 32 AF XY: 0.164 AC XY: 12189 AN XY: 74368

African (AFR) AF: 0.123 AC: 5119 AN: 41504

American (AMR) AF: 0.141 AC: 2160 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3470

East Asian (EAS) AF: 0.0401 AC: 208 AN: 5182

South Asian (SAS) AF: 0.211 AC: 1016 AN: 4826

European-Finnish (FIN) AF: 0.187 AC: 1977 AN: 10574

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13494 AN: 67962

Other (OTH) AF: 0.158 AC: 334 AN: 2112

Alfa AF: 0.186 Hom.: 482

Bravo AF: 0.157

Asia WGS AF: 0.125 AC: 434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.52
PhyloP100		0.21
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: rs12706341; hg19: chr7-121024708;