rs799493

Variant names:

• chr14-35082669-T-C
• rs799493
• NM_173607.5:c.*1441T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173607.5(FAM177A1):​c.*1441T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,118 control chromosomes in the GnomAD database, including 4,023 homozygotes. 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: 𝑓 0.21 (4023 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: FAM177A1 NM_173607.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.614
• Publications: 9 publications found

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]

FAM177A1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics, G2P

LOC101927178 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM177A1	NM_173607.5	c.*1441T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000280987.9	NP_775878.2
FAM177A1	NM_001079519.1	c.*1441T>C		3_prime_UTR_variant	Exon 7 of 7		NP_001072987.1
FAM177A1	NM_001289022.3	c.*1441T>C		3_prime_UTR_variant	Exon 6 of 6		NP_001275951.1
LOC101927178	NR_110415.1	n.479+1110T>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM177A1	ENST00000280987.9	c.*1441T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_173607.5	ENSP00000280987.4

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31864 AN: 152000 Hom.: 4027 Cov.: 32

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.0699

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.234

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.209 AC: 31863 AN: 152118 Hom.: 4023 Cov.: 32 AF XY: 0.204 AC XY: 15200 AN XY: 74346

African (AFR) AF: 0.0817 AC: 3394 AN: 41536

American (AMR) AF: 0.209 AC: 3189 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3468

East Asian (EAS) AF: 0.0699 AC: 362 AN: 5182

South Asian (SAS) AF: 0.145 AC: 700 AN: 4824

European-Finnish (FIN) AF: 0.250 AC: 2636 AN: 10558

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19668 AN: 67980

Other (OTH) AF: 0.232 AC: 488 AN: 2104

Alfa AF: 0.248 Hom.: 1975

Bravo AF: 0.203

Asia WGS AF: 0.104 AC: 359 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.79
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs799493; hg19: chr14-35551875;