chr20-56525967-C-A

Position:

• chr20-56525967-C-A

Variant summary

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

The NM_001012971.4(FAM209A):​c.413C>A​(p.Ala138Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM209A NM_001012971.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.668

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=0.3081156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM209A	NM_001012971.4	c.413C>A	p.Ala138Glu	missense_variant	2/2	ENST00000371328.5	NP_001012989.2
FAM209A	XM_047439964.1	c.413C>A	p.Ala138Glu	missense_variant	2/5		XP_047295920.1
FAM209A	XM_047439965.1	c.413C>A	p.Ala138Glu	missense_variant	2/6		XP_047295921.1
GCNT7	NR_160308.1	n.-42G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM209A	ENST00000371328.5	c.413C>A	p.Ala138Glu	missense_variant	2/2	1	NM_001012971.4	ENSP00000360379.4
FAM209A	ENST00000481560.1	n.558C>A		non_coding_transcript_exon_variant	4/4	5
GCNT7	ENST00000243913.8	c.-1114G>T		upstream_gene_variant		2		ENSP00000243913.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 28, 2022

The c.413C>A (p.A138E) alteration is located in exon 2 (coding exon 2) of the FAM209A gene. This alteration results from a C to A substitution at nucleotide position 413, causing the alanine (A) at amino acid position 138 to be replaced by a glutamic acid (E). 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	0.21
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.095
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.48
MutPred		0.35		Gain of solvent accessibility (P = 0.0145);
MVP		0.12
MPC		0.88
ClinPred		0.94	D
GERP RS		3.3
Varity_R		0.55
gMVP		0.17

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: chr20-55101023;