NM_173607.5:c.166-3T>C

Variant names:

• chr14-35053275-T-C
• rs61754299
• NM_173607.5:c.166-3T>C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_173607.5(FAM177A1):​c.166-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,606,138 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (25 hom.)
• Consequence: FAM177A1 NM_173607.5 splice_region, intron
• Scores: Splicing: ADA: 0.00002512
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High Homozygotes in GnomAdExome4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM177A1	NM_173607.5	c.166-3T>C		splice_region_variant, intron_variant	Intron 1 of 4	ENST00000280987.9	NP_775878.2
FAM177A1	NM_001079519.1	c.97-3T>C		splice_region_variant, intron_variant	Intron 3 of 6		NP_001072987.1
FAM177A1	NM_001289022.3	c.97-3T>C		splice_region_variant, intron_variant	Intron 2 of 5		NP_001275951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM177A1	ENST00000280987.9	c.166-3T>C		splice_region_variant, intron_variant	Intron 1 of 4	1	NM_173607.5	ENSP00000280987.4

Frequencies

GnomAD3 genomes AF: 0.00274 AC: 417 AN: 152192 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00432

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00240 AC: 586 AN: 244300 Hom.: 1 AF XY: 0.00241 AC XY: 319 AN XY: 132552

Gnomad AFR exome AF: 0.000753

Gnomad AMR exome AF: 0.00132

Gnomad ASJ exome AF: 0.00356

Gnomad EAS exome AF: 0.000335

Gnomad SAS exome AF: 0.000136

Gnomad FIN exome AF: 0.000325

Gnomad NFE exome AF: 0.00414

Gnomad OTH exome AF: 0.00285

GnomAD4 exome AF: 0.00430 AC: 6245 AN: 1453828 Hom.: 25 Cov.: 30 AF XY: 0.00414 AC XY: 2997 AN XY: 723524

Gnomad4 AFR exome AF: 0.000643

Gnomad4 AMR exome AF: 0.00176

Gnomad4 ASJ exome AF: 0.00382

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.000224

Gnomad4 FIN exome AF: 0.000694

Gnomad4 NFE exome AF: 0.00513

Gnomad4 OTH exome AF: 0.00479

GnomAD4 genome AF: 0.00273 AC: 416 AN: 152310 Hom.: 1 Cov.: 32 AF XY: 0.00247 AC XY: 184 AN XY: 74478

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000754

Gnomad4 NFE AF: 0.00432

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00330 Hom.: 0

Bravo AF: 0.00309

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00518

EpiControl AF: 0.00474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.014
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: rs61754299; hg19: chr14-35522481;