chr7-121378916-G-C

Position:

• chr7-121378916-G-C

Variant summary

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

The NM_014888.3(FAM3C):​c.112C>G​(p.Leu38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
• Consequence: FAM3C NM_014888.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65

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=0.10146648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM3C	NM_014888.3	c.112C>G	p.Leu38Val	missense_variant	3/10	ENST00000359943.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM3C	ENST00000359943.8	c.112C>G	p.Leu38Val	missense_variant	3/10	1	NM_014888.3	P1
FAM3C	ENST00000412653.5	c.112C>G	p.Leu38Val	missense_variant	3/8	4
FAM3C	ENST00000426156.1	c.22C>G	p.Leu8Val	missense_variant	4/9	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 19

GnomAD4 genome Cov.: 31

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

Sep 14, 2023

The c.112C>G (p.L38V) alteration is located in exon 3 (coding exon 2) of the FAM3C gene. This alteration results from a C to G substitution at nucleotide position 112, causing the leucine (L) at amino acid position 38 to be replaced by a valine (V). 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	0.091
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.026	T;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;.
MutationTaster	Benign	0.57	D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.20	N;N;N
REVEL	Benign	0.019
Sift	Benign	0.44	T;T;T
Sift4G	Benign	0.54	T;.;.
Polyphen		0.0040	B;.;.
Vest4		0.24
MutPred		0.24		Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);.;
MVP		0.48
MPC		0.51
ClinPred		0.28	T
GERP RS		4.5
Varity_R		0.074
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-121018970;