6-4068733-G-C

Variant names:

• chr6-4068733-G-C
• NM_173563.3:c.1490C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173563.3(FAM217A):​c.1490C>G​(p.Ala497Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 6.9e-7 (0 hom.)
• Consequence: FAM217A NM_173563.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.156

Genes affected

FAM217A (HGNC:21362): (family with sequence similarity 217 member A)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048582852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM217A	NM_173563.3	c.1490C>G	p.Ala497Gly	missense_variant	Exon 7 of 7	ENST00000274673.8	NP_775834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM217A	ENST00000274673.8	c.1490C>G	p.Ala497Gly	missense_variant	Exon 7 of 7	1	NM_173563.3	ENSP00000274673.3
FAM217A	ENST00000639338.1	c.1892C>G	p.Ala631Gly	missense_variant	Exon 9 of 9	5		ENSP00000492773.1
FAM217A	ENST00000380188.2	n.1899C>G		non_coding_transcript_exon_variant	Exon 5 of 5	2
FAM217A	ENST00000469157.5	n.391+4542C>G		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459656 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726014

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

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

Jan 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1490C>G (p.A497G) alteration is located in exon 7 (coding exon 6) of the FAM217A gene. This alteration results from a C to G substitution at nucleotide position 1490, causing the alanine (A) at amino acid position 497 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	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.5
DANN	Benign	0.96
DEOGEN2	Benign	0.0053	T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.83	L;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N;.
REVEL	Benign	0.049
Sift	Benign	0.22	T;.
Sift4G	Benign	0.10	T;.
Polyphen		0.0080	B;.
Vest4		0.093
MutPred		0.24		Loss of catalytic residue at A497 (P = 0.0411);.;
MVP		0.048
MPC		0.032
ClinPred		0.037	T
GERP RS		0.99
Varity_R		0.052
gMVP		0.028

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: chr6-4068967;