7-121359967-A-ATTT

Variant names:

• chr7-121359967-A-ATTT
• rs3837124
• NM_014888.3:c.467+73_467+75dupAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014888.3(FAM3C):​c.467+73_467+75dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000826 in 605,276 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: FAM3C NM_014888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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+73_467+75dupAAA		intron	N/A	NP_055703.1
	FAM3C	NM_001040020.2		c.467+73_467+75dupAAA		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+76insAAA		intron	N/A	ENSP00000353025.3
	FAM3C	ENST00000850865.1		c.467+75_467+76insAAA		intron	N/A	ENSP00000520951.1
	FAM3C	ENST00000412653.5	TSL:4	c.*88_*89insAAA		downstream_gene	N/A	ENSP00000408636.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000826 AC: 5 AN: 605276 Hom.: 0 AF XY: 0.0000123 AC XY: 4 AN XY: 326502

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000170 AC: 2 AN: 11796

American (AMR) AF: 0.00 AC: 0 AN: 31874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18624

East Asian (EAS) AF: 0.00 AC: 0 AN: 33780

South Asian (SAS) AF: 0.00 AC: 0 AN: 58162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2848

European-Non Finnish (NFE) AF: 0.00000801 AC: 3 AN: 374522

Other (OTH) AF: 0.00 AC: 0 AN: 30462

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3837124; hg19: chr7-121000021;