17-49711400-C-T

Variant names:

• chr17-49711400-C-T
• NM_030802.4:c.1217G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030802.4(FAM117A):​c.1217G>A​(p.Gly406Glu) 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. 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)
• Consequence: FAM117A NM_030802.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12015468).

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.1217G>A	p.Gly406Glu	missense	Exon 8 of 8	NP_110429.1	Q9C073-1
	FAM117A	NM_001411126.1		c.401G>A	p.Gly134Glu	missense	Exon 8 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.1217G>A	p.Gly406Glu	missense	Exon 8 of 8	ENSP00000240364.2	Q9C073-1
	FAM117A	ENST00000513602.5	TSL:2	c.401G>A	p.Gly134Glu	missense	Exon 8 of 8	ENSP00000465808.1	Q9C073-2
	FAM117A	ENST00000503573.5	TSL:5	n.*553G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000467070.1	K7ENS5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.18
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.2
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.076
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.27	T
Polyphen		0.20	B
Vest4		0.40
MutPred		0.064		Gain of solvent accessibility (P = 0.024)
MVP		0.048
MPC		1.4
ClinPred		0.63	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.096
gMVP		0.18

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: chr17-47788762;