rs749711689

Variant names:

• chr17-49720346-C-A
• rs749711689
• NM_030802.4:c.553G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-49720346-C-A
• chr17-49720346-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.553G>T​(p.Ala185Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,364 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. 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. A185T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: FAM117A NM_030802.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.658

Genes affected

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

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=0.08248466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM117A	NM_030802.4	c.553G>T	p.Ala185Ser	missense_variant	Exon 4 of 8	ENST00000240364.7	NP_110429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM117A	ENST00000240364.7	c.553G>T	p.Ala185Ser	missense_variant	Exon 4 of 8	1	NM_030802.4	ENSP00000240364.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 250806 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135568

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461364 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727010

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000671

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: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000306 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	T;T;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.082	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.044
Sift	Benign	0.27	T;D;T
Sift4G	Benign	0.31	T;.;.
Polyphen		0.78	P;.;.
Vest4		0.41
MutPred		0.27		Gain of phosphorylation at A185 (P = 0.0128);.;.;
MVP		0.092
MPC		0.59
ClinPred		0.38	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.044
gMVP		0.16

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: rs749711689; hg19: chr17-47797708;