20-56524854-T-G

Variant names:

• chr20-56524854-T-G
• NM_001012971.4:c.46T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001012971.4(FAM209A):​c.46T>G​(p.Cys16Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FAM209A NM_001012971.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

Genes affected

FAM209A (HGNC:16100): (family with sequence similarity 209 member A) Located in extracellular exosome and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

GCNT7 (HGNC:16099): (glucosaminyl (N-acetyl) transferase family member 7) Predicted to enable acetylglucosaminyltransferase activity. Predicted to be involved in protein glycosylation. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34258878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM209A	NM_001012971.4	c.46T>G	p.Cys16Gly	missense_variant	Exon 1 of 2	ENST00000371328.5	NP_001012989.2
FAM209A	XM_047439964.1	c.46T>G	p.Cys16Gly	missense_variant	Exon 1 of 5		XP_047295920.1
FAM209A	XM_047439965.1	c.46T>G	p.Cys16Gly	missense_variant	Exon 1 of 6		XP_047295921.1
GCNT7	NR_160308.1	n.143+929A>C		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM209A	ENST00000371328.5	c.46T>G	p.Cys16Gly	missense_variant	Exon 1 of 2	1	NM_001012971.4	ENSP00000360379.4
GCNT7	ENST00000243913.8	c.-930+929A>C		intron_variant	Intron 1 of 6	2		ENSP00000243913.4
FAM209A	ENST00000481560.1	n.227-36T>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

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

Feb 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.46T>G (p.C16G) alteration is located in exon 1 (coding exon 1) of the FAM209A gene. This alteration results from a T to G substitution at nucleotide position 46, causing the cysteine (C) at amino acid position 16 to be replaced by a glycine (G). 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	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.87
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PROVEAN	Pathogenic	-7.9	D
REVEL	Benign	0.094
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.046	D
Polyphen		0.022	B
Vest4		0.50
MutPred		0.63		Gain of loop (P = 0.0312);
MVP		0.12
MPC		0.87
ClinPred		0.43	T
GERP RS		3.3
Varity_R		0.38
gMVP		0.096

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-55099910;