Genetic Variant FAM177A1:p.Asn58Asn (chr14-35053286-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_173607.5(FAM177A1):c.174C>T(p.Asn58Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,609,392 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 12 hom. )

Consequence

FAM177A1
NM_173607.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.122

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 14-35053286-C-T is Benign according to our data. Variant chr14-35053286-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 729468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.122 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0011 (1607/1457226) while in subpopulation MID AF= 0.0247 (142/5754). AF 95% confidence interval is 0.0214. There are 12 homozygotes in gnomad4_exome. There are 859 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM177A1	NM_173607.5 link	c.174C>T	p.Asn58Asn	synonymous_variant	Exon 2 of 5	ENST00000280987.9	NP_775878.2	Q8N128-2
FAM177A1	NM_001079519.1 link	c.105C>T	p.Asn35Asn	synonymous_variant	Exon 4 of 7		NP_001072987.1	Q8N128-1
FAM177A1	NM_001289022.3 link	c.105C>T	p.Asn35Asn	synonymous_variant	Exon 3 of 6		NP_001275951.1	Q8N128-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM177A1	ENST00000280987.9 link	c.174C>T	p.Asn58Asn	synonymous_variant	Exon 2 of 5	1	NM_173607.5	ENSP00000280987.4		Q8N128-2

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

165

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00133

AC:

328

AN:

247318

Hom.:

AF XY:

0.00155

AC XY:

208

AN XY:

133932

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.000761

Gnomad ASJ exome

AF:

0.00412

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00330

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.00129

Gnomad OTH exome

AF:

0.00215

GnomAD4 exome

AF:

0.00110

AC:

1607

AN:

1457226

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

859

AN XY:

725080

show subpopulations

Gnomad4 AFR exome

AF:

0.000758

Gnomad4 AMR exome

AF:

0.000887

Gnomad4 ASJ exome

AF:

0.00381

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00337

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000802

Gnomad4 OTH exome

AF:

0.00193

GnomAD4 genome

AF:

0.00108

AC:

165

AN:

152166

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.00132

EpiCase

AF:

0.00164

EpiControl

AF:

0.00172

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FAM177A1: BP4, BP7 -

Jun 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.0

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over