17-49716240-C-G

Variant names:

• chr17-49716240-C-G
• rs2073502732
• NM_030802.4:c.986G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030802.4(FAM117A):​c.986G>C​(p.Arg329Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R329Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM117A NM_030802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 0 publications found

Genes affected

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

ENSG00000250751 (HGNC:):

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=0.28043133).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030802.4. 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
	FAM117A	NM_030802.4	MANE Select	c.986G>C	p.Arg329Pro	missense	Exon 7 of 8	NP_110429.1	Q9C073-1
	FAM117A	NM_001411126.1		c.170G>C	p.Arg57Pro	missense	Exon 7 of 8	NP_001398055.1	Q9C073-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM117A	ENST00000240364.7	TSL:1 MANE Select	c.986G>C	p.Arg329Pro	missense	Exon 7 of 8	ENSP00000240364.2	Q9C073-1
	FAM117A	ENST00000511743.5	TSL:3	c.656G>C	p.Arg219Pro	missense	Exon 6 of 6	ENSP00000427326.1	D6RJ87
	FAM117A	ENST00000513602.5	TSL:2	c.170G>C	p.Arg57Pro	missense	Exon 7 of 8	ENSP00000465808.1	Q9C073-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.3
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.97	D
Vest4		0.47
MutPred		0.26		Gain of glycosylation at R329 (P = 0.0031)
MVP		0.12
MPC		1.5
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.67
gMVP		0.78

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

Other links and lift over

dbSNP: rs2073502732; hg19: chr17-47793602;