dbSNP rs1336465620: FAM177A1:p.Glu180Ala (chr14-35081056-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_173607.5(FAM177A1):c.539A>C(p.Glu180Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E180D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FAM177A1
NM_173607.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.33

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics, G2P

FAM177A1 links:

LOC101927178 (HGNC:):

LOC101927178 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30983007).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173607.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM177A1	NM_173607.5	MANE Select	c.539A>C	p.Glu180Ala	missense	Exon 5 of 5	NP_775878.2	Q8N128-2
FAM177A1	NM_001079519.1		c.470A>C	p.Glu157Ala	missense	Exon 7 of 7	NP_001072987.1	Q8N128-1
FAM177A1	NM_001289022.3		c.470A>C	p.Glu157Ala	missense	Exon 6 of 6	NP_001275951.1	Q8N128-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM177A1	ENST00000280987.9	TSL:1 MANE Select	c.539A>C	p.Glu180Ala	missense	Exon 5 of 5	ENSP00000280987.4	Q8N128-2
FAM177A1	ENST00000382406.7	TSL:1	c.470A>C	p.Glu157Ala	missense	Exon 6 of 6	ENSP00000371843.3	Q8N128-1
FAM177A1	ENST00000555211.6	TSL:4	c.470A>C	p.Glu157Ala	missense	Exon 7 of 7	ENSP00000451508.2	Q8N128-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

249958

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726256

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33430

American (AMR)

AF:

0.00

AC:

AN:

44512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39616

South Asian (SAS)

AF:

0.00

AC:

AN:

85916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5364

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111316

Other (OTH)

AF:

0.00

AC:

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0059

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.5

PhyloP100

6.3

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.9

REVEL

Benign

0.17

Sift

Benign

0.042

Sift4G

Benign

0.11

Polyphen

0.99

Vest4

0.37

MutPred

0.088

Gain of helix (P = 0.062)

MVP

0.67

MPC

0.089

ClinPred

0.93

GERP RS

5.3

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.7

Varity_R

0.16

gMVP

0.59

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over