7-121362539-T-C

Variant names:

• chr7-121362539-T-C
• rs2536165
• NM_014888.3:c.382+358A>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.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
• Publications: 2 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 = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM3C	NM_014888.3	c.382+358A>G		intron_variant	Intron 7 of 9	ENST00000359943.8	NP_055703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM3C	ENST00000359943.8	c.382+358A>G		intron_variant	Intron 7 of 9	1	NM_014888.3	ENSP00000353025.3

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

African (AFR) AF: 0.434 AC: 17983 AN: 41410

American (AMR) AF: 0.173 AC: 2645 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 532 AN: 3466

East Asian (EAS) AF: 0.0405 AC: 210 AN: 5190

South Asian (SAS) AF: 0.211 AC: 1014 AN: 4814

European-Finnish (FIN) AF: 0.186 AC: 1957 AN: 10534

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13572 AN: 67924

Other (OTH) AF: 0.229 AC: 485 AN: 2116

Alfa AF: 0.168 Hom.: 519

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
PhyloP100		-1.3
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: rs2536165; hg19: chr7-121002593;