17-49716240-C-T

Position:

• chr17-49716240-C-T

Variant summary

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

The NM_030802.4(FAM117A):​c.986G>A​(p.Arg329Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,192 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: FAM117A NM_030802.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32

Genes affected

FAM117A (HGNC:24179): (family with sequence similarity 117 member A)

ENSG00000250751 (HGNC:):

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=0.12472084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM117A	NM_030802.4	c.986G>A	p.Arg329Gln	missense_variant	7/8	ENST00000240364.7	NP_110429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM117A	ENST00000240364.7	c.986G>A	p.Arg329Gln	missense_variant	7/8	1	NM_030802.4	ENSP00000240364.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1460192 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 726458

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Apr 01, 2024

The c.986G>A (p.R329Q) alteration is located in exon 7 (coding exon 7) of the FAM117A gene. This alteration results from a G to A substitution at nucleotide position 986, causing the arginine (R) at amino acid position 329 to be replaced by a glutamine (Q). 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	0.084
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	T;.;T
Eigen	Benign	-0.020
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.86	D;D;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N;.;N
REVEL	Benign	0.058
Sift	Benign	0.14	T;.;D
Sift4G	Uncertain	0.022	D;D;.
Polyphen		0.27	B;.;.
Vest4		0.16
MutPred		0.15		Loss of methylation at R329 (P = 0.0778);.;.;
MVP		0.076
MPC		0.56
ClinPred		0.82	D
GERP RS		4.6
Varity_R		0.12
gMVP		0.53

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: rs2073502732; hg19: chr17-47793602; COSMIC: COSV53631640; COSMIC: COSV53631640;