NM_173607.5:c.539A>C

Variant names:

• chr14-35081056-A-C
• rs1336465620
• NM_173607.5:c.539A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173607.5(FAM177A1):​c.539A>C​(p.Glu180Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,916 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.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FAM177A1 NM_173607.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.33

Genes affected

FAM177A1 (HGNC:19829): (family with sequence similarity 177 member A1) This gene encodes a member of a conserved protein family. Alternative splicing results in multiple transcript variants. This gene is thought to be associated with susceptibility to juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]

LOC101927178 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30983007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM177A1	NM_173607.5	c.539A>C	p.Glu180Ala	missense_variant	Exon 5 of 5	ENST00000280987.9	NP_775878.2
FAM177A1	NM_001079519.1	c.470A>C	p.Glu157Ala	missense_variant	Exon 7 of 7		NP_001072987.1
FAM177A1	NM_001289022.3	c.470A>C	p.Glu157Ala	missense_variant	Exon 6 of 6		NP_001275951.1
LOC101927178	NR_110415.1	n.-25A>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM177A1	ENST00000280987.9	c.539A>C	p.Glu180Ala	missense_variant	Exon 5 of 5	1	NM_173607.5	ENSP00000280987.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249958 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135108

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459916 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726256

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T;T;.;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D;.;D;D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.5	M;M;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.042	D;D;D;D
Sift4G	Benign	0.11	T;T;T;T
Polyphen		0.99	D;D;D;.
Vest4		0.37
MutPred		0.088		Gain of helix (P = 0.062);Gain of helix (P = 0.062);.;.;
MVP		0.67
MPC		0.089
ClinPred		0.93	D
GERP RS		5.3
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.7
Varity_R		0.16
gMVP		0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs1336465620; hg19: chr14-35550262;