rs368889183

Variant names:

• chr17-49719854-C-A
• rs368889183
• NM_030802.4:c.614G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-49719854-C-A
• chr17-49719854-C-T

Variant summary

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

The NM_030802.4(FAM117A):​c.614G>T​(p.Arg205Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,206 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R205Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM117A NM_030802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.614G>T	p.Arg205Leu	missense	Exon 5 of 8	NP_110429.1	Q9C073-1
	FAM117A	NM_001411126.1		c.-203G>T		5_prime_UTR	Exon 5 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.614G>T	p.Arg205Leu	missense	Exon 5 of 8	ENSP00000240364.2	Q9C073-1
	FAM117A	ENST00000511743.5	TSL:3	c.284G>T	p.Arg95Leu	missense	Exon 4 of 6	ENSP00000427326.1	D6RJ87
	FAM117A	ENST00000506156.1	TSL:3	c.518G>T	p.Arg173Leu	missense	Exon 4 of 5	ENSP00000421412.1	D6RFX7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455206 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724032

African (AFR) AF: 0.00 AC: 0 AN: 33032

American (AMR) AF: 0.00 AC: 0 AN: 42978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25886

East Asian (EAS) AF: 0.00 AC: 0 AN: 39274

South Asian (SAS) AF: 0.00 AC: 0 AN: 85344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109996

Other (OTH) AF: 0.00 AC: 0 AN: 60124

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.14
Sift	Benign	0.072	T
Sift4G	Benign	0.087	T
Polyphen		0.99	D
Vest4		0.66
MutPred		0.34		Loss of disorder (P = 0.0467)
MVP		0.055
MPC		1.4
ClinPred		0.97	D
GERP RS		4.1
Varity_R		0.15
gMVP		0.41
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.45		Position offset: -7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs368889183; hg19: chr17-47797216;