7-121382963-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014888.3(FAM3C):c.7G>A(p.Val3Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM3C NM_014888.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098641306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM3C	NM_014888.3	c.7G>A	p.Val3Ile	missense_variant	2/10	ENST00000359943.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM3C	ENST00000359943.8	c.7G>A	p.Val3Ile	missense_variant	2/10	1	NM_014888.3	P1
FAM3C	ENST00000412653.5	c.7G>A	p.Val3Ile	missense_variant	2/8	4
FAM3C	ENST00000426156.1	c.-140G>A		5_prime_UTR_variant	2/9	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449824 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 721654

Gnomad4 AFR exome AF: 0.0000303

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.7G>A (p.V3I) alteration is located in exon 2 (coding exon 1) of the FAM3C gene. This alteration results from a G to A substitution at nucleotide position 7, causing the valine (V) at amino acid position 3 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	20
Dann	Benign	0.95
DEOGEN2	Benign	0.033	T;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.099	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	N;.
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.16
Sift	Benign	0.30	T;T
Sift4G	Benign	0.40	T;.
Polyphen		0.0	B;.
Vest4		0.28
MVP		0.44
MPC		0.41
ClinPred		0.19	T
GERP RS		4.1
Varity_R		0.051
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-121023017;