20-56524980-A-G

Variant names:

• chr20-56524980-A-G
• rs1600846447
• NM_001012971.4:c.172A>G

Variant summary

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

The NM_001012971.4(FAM209A):​c.172A>G​(p.Ser58Gly) 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: 2.52

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24037504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM209A	NM_001012971.4	c.172A>G	p.Ser58Gly	missense_variant	Exon 1 of 2	ENST00000371328.5	NP_001012989.2
FAM209A	XM_047439964.1	c.172A>G	p.Ser58Gly	missense_variant	Exon 1 of 5		XP_047295920.1
FAM209A	XM_047439965.1	c.172A>G	p.Ser58Gly	missense_variant	Exon 1 of 6		XP_047295921.1
GCNT7	NR_160308.1	n.143+803T>C		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM209A	ENST00000371328.5	c.172A>G	p.Ser58Gly	missense_variant	Exon 1 of 2	1	NM_001012971.4	ENSP00000360379.4
GCNT7	ENST00000243913.8	c.-930+803T>C		intron_variant	Intron 1 of 6	2		ENSP00000243913.4
FAM209A	ENST00000481560.1	n.317A>G		non_coding_transcript_exon_variant	Exon 3 of 4	5

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

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.172A>G (p.S58G) alteration is located in exon 1 (coding exon 1) of the FAM209A gene. This alteration results from a A to G substitution at nucleotide position 172, causing the serine (S) at amino acid position 58 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	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.043	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.058
Sift	Benign	0.14	T
Sift4G	Uncertain	0.052	T
Polyphen		0.88	P
Vest4		0.27
MutPred		0.23		Gain of sheet (P = 0.039);
MVP		0.28
MPC		0.21
ClinPred		0.69	D
GERP RS		5.5
Varity_R		0.17
gMVP		0.084

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

LitVar

Other links and lift over

dbSNP: rs1600846447; hg19: chr20-55100036;