rs2536182

Variant names:

• chr7-121350783-C-G
• rs2536182
• NM_014888.3:c.595-233G>C

Variant summary

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

The NM_014888.3(FAM3C):​c.595-233G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,990 control chromosomes in the GnomAD database, including 21,818 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 0.51 (21818 hom., cov: 32)
• Consequence: FAM3C NM_014888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM3C	NM_014888.3	c.595-233G>C		intron_variant	Intron 9 of 9	ENST00000359943.8	NP_055703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM3C	ENST00000359943.8	c.595-233G>C		intron_variant	Intron 9 of 9	1	NM_014888.3	ENSP00000353025.3
FAM3C	ENST00000850865.1	c.595-233G>C		intron_variant	Intron 9 of 9			ENSP00000520951.1
FAM3C	ENST00000474082.1	n.400-233G>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77765 AN: 151872 Hom.: 21781 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.512 AC: 77856 AN: 151990 Hom.: 21818 Cov.: 32 AF XY: 0.499 AC XY: 37025 AN XY: 74252

African (AFR) AF: 0.744 AC: 30836 AN: 41474

American (AMR) AF: 0.417 AC: 6360 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1581 AN: 3466

East Asian (EAS) AF: 0.132 AC: 683 AN: 5178

South Asian (SAS) AF: 0.276 AC: 1332 AN: 4820

European-Finnish (FIN) AF: 0.404 AC: 4260 AN: 10532

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31269 AN: 67940

Other (OTH) AF: 0.494 AC: 1044 AN: 2112

Alfa AF: 0.510 Hom.: 2568

Bravo AF: 0.527

Asia WGS AF: 0.282 AC: 979 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.59
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: rs2536182; hg19: chr7-120990837;