NM_001012971.4:c.46T>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 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: 6.8e-7 (0 hom.)
• Consequence: FAM209A NM_001012971.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012971.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM209A	NM_001012971.4	MANE Select	c.46T>G	p.Cys16Gly	missense	Exon 1 of 2	NP_001012989.2	Q5JX71
	GCNT7	NR_160308.1		n.143+929A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM209A	ENST00000371328.5	TSL:1 MANE Select	c.46T>G	p.Cys16Gly	missense	Exon 1 of 2	ENSP00000360379.4	Q5JX71
	GCNT7	ENST00000243913.8	TSL:2	c.-930+929A>C		intron	N/A	ENSP00000243913.4	Q6ZNI0
	FAM209A	ENST00000481560.1	TSL:5	n.227-36T>G		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		2.1
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
PromoterAI		0.031	Neutral
Varity_R		0.38
gMVP		0.096
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

hg19: chr20-55099910;