Genetic Variant FAM177A1:p.Thr23Thr (chr14-35046532-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_173607.5(FAM177A1):c.69G>A(p.Thr23Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,602,436 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 18 hom. )

Consequence

FAM177A1
NM_173607.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.259

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 14-35046532-G-A is Benign according to our data. Variant chr14-35046532-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3770437.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.259 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM177A1	NM_173607.5 link	c.69G>A	p.Thr23Thr	synonymous_variant	Exon 1 of 5	ENST00000280987.9	NP_775878.2	Q8N128-2
FAM177A1	NM_001079519.1 link	c.-1G>A		5_prime_UTR_variant	Exon 3 of 7		NP_001072987.1	Q8N128-1
FAM177A1	NM_001289022.3 link	c.-1G>A		5_prime_UTR_variant	Exon 2 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.69G>A	p.Thr23Thr	synonymous_variant	Exon 1 of 5	1	NM_173607.5	ENSP00000280987.4		Q8N128-2

Frequencies

GnomAD3 genomes

AF:

0.00336

AC:

512

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00492

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00315

AC:

726

AN:

230668

Hom.:

AF XY:

0.00323

AC XY:

406

AN XY:

125734

show subpopulations

Gnomad AFR exome

AF:

0.000795

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000604

Gnomad FIN exome

AF:

0.00253

Gnomad NFE exome

AF:

0.00524

Gnomad OTH exome

AF:

0.00323

GnomAD4 exome

AF:

0.00442

AC:

6415

AN:

1450102

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

3084

AN XY:

720608

show subpopulations

Gnomad4 AFR exome

AF:

0.000759

Gnomad4 AMR exome

AF:

0.00249

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000689

Gnomad4 FIN exome

AF:

0.00334

Gnomad4 NFE exome

AF:

0.00524

Gnomad4 OTH exome

AF:

0.00370

GnomAD4 genome

AF:

0.00335

AC:

511

AN:

152334

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

253

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.00492

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00357

Hom.:

Bravo

AF:

0.00313

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FAM177A1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

9.6

DANN

Benign

0.86

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

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