7-121359967-A-AT

Variant names:

• chr7-121359967-A-AT
• rs3837124
• NM_014888.3:c.467+75dupA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_014888.3(FAM3C):​c.467+75dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 750,732 control chromosomes in the GnomAD database, including 57,360 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (24493 hom., cov: 0)
  • Exomes 𝑓: 0.38 (32867 hom.)
• Consequence: FAM3C NM_014888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014888.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM3C	NM_014888.3	MANE Select	c.467+75dupA		intron	N/A	NP_055703.1
	FAM3C	NM_001040020.2		c.467+75dupA		intron	N/A	NP_001035109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM3C	ENST00000359943.8	TSL:1 MANE Select	c.467+75_467+76insA		intron	N/A	ENSP00000353025.3
	FAM3C	ENST00000850865.1		c.467+75_467+76insA		intron	N/A	ENSP00000520951.1
	FAM3C	ENST00000412653.5	TSL:4	c.*88_*89insA		downstream_gene	N/A	ENSP00000408636.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 81914 AN: 150660 Hom.: 24455 Cov.: 0

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.380 AC: 227776 AN: 599964 Hom.: 32867 AF XY: 0.381 AC XY: 123175 AN XY: 323692

African (AFR) AF: 0.678 AC: 7969 AN: 11752

American (AMR) AF: 0.336 AC: 10607 AN: 31554

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 7388 AN: 18466

East Asian (EAS) AF: 0.144 AC: 4814 AN: 33428

South Asian (SAS) AF: 0.369 AC: 21235 AN: 57596

European-Finnish (FIN) AF: 0.377 AC: 16176 AN: 42860

Middle Eastern (MID) AF: 0.408 AC: 1146 AN: 2812

European-Non Finnish (NFE) AF: 0.394 AC: 146374 AN: 371314

Other (OTH) AF: 0.400 AC: 12067 AN: 30182

GnomAD4 genome AF: 0.544 AC: 82001 AN: 150768 Hom.: 24493 Cov.: 0 AF XY: 0.532 AC XY: 39183 AN XY: 73606

African (AFR) AF: 0.808 AC: 33204 AN: 41072

American (AMR) AF: 0.432 AC: 6533 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1620 AN: 3458

East Asian (EAS) AF: 0.165 AC: 853 AN: 5156

South Asian (SAS) AF: 0.424 AC: 2028 AN: 4788

European-Finnish (FIN) AF: 0.409 AC: 4199 AN: 10260

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.473 AC: 31990 AN: 67612

Other (OTH) AF: 0.518 AC: 1080 AN: 2084

Alfa AF: 0.363 Hom.: 863

Bravo AF: 0.559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.46
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: rs3837124; hg19: chr7-121000021; COSMIC: COSV106063154; COSMIC: COSV106063154;