NM_173607.5:c.386C>T

Variant names:

• chr14-35077196-C-T
• rs769436856
• NM_173607.5:c.386C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173607.5(FAM177A1):​c.386C>T​(p.Ala129Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,722 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.

• 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: 4.51

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]

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=0.12545913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM177A1	NM_173607.5	c.386C>T	p.Ala129Val	missense_variant	Exon 3 of 5	ENST00000280987.9	NP_775878.2
FAM177A1	NM_001079519.1	c.317C>T	p.Ala106Val	missense_variant	Exon 5 of 7		NP_001072987.1
FAM177A1	NM_001289022.3	c.317C>T	p.Ala106Val	missense_variant	Exon 4 of 6		NP_001275951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM177A1	ENST00000280987.9	c.386C>T	p.Ala129Val	missense_variant	Exon 3 of 5	1	NM_173607.5	ENSP00000280987.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251386 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135860

Gnomad AFR exome AF: 0.0000615

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461722 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727156

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

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	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Benign	0.38
DEOGEN2	Benign	0.0079	T;T;.;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.077
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.94	D;.;D;D
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.23	N;N;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.40	N;N;N;N
REVEL	Benign	0.080
Sift	Benign	0.90	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.14	B;B;B;.
Vest4		0.20
MutPred		0.33		Gain of catalytic residue at S109 (P = 0);Gain of catalytic residue at S109 (P = 0);.;.;
MVP		0.48
MPC		0.019
ClinPred		0.31	T
GERP RS		5.6
Varity_R		0.042
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs769436856; hg19: chr14-35546402;