NM_173607.5:c.81G>T

Variant names:

• chr14-35046544-G-T
• rs201860851
• NM_173607.5:c.81G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173607.5(FAM177A1):​c.81G>T​(p.Glu27Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,600,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: FAM177A1 NM_173607.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.457
• Publications: 0 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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022470474).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM177A1	NM_173607.5	MANE Select	c.81G>T	p.Glu27Asp	missense	Exon 1 of 5	NP_775878.2	Q8N128-2
	FAM177A1	NM_001079519.1		c.12G>T	p.Glu4Asp	missense	Exon 3 of 7	NP_001072987.1	Q8N128-1
	FAM177A1	NM_001289022.3		c.12G>T	p.Glu4Asp	missense	Exon 2 of 6	NP_001275951.1	Q8N128-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM177A1	ENST00000280987.9	TSL:1 MANE Select	c.81G>T	p.Glu27Asp	missense	Exon 1 of 5	ENSP00000280987.4	Q8N128-2
	FAM177A1	ENST00000382406.7	TSL:1	c.12G>T	p.Glu4Asp	missense	Exon 2 of 6	ENSP00000371843.3	Q8N128-1
	FAM177A1	ENST00000555211.6	TSL:4	c.12G>T	p.Glu4Asp	missense	Exon 3 of 7	ENSP00000451508.2	Q8N128-1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000532 AC: 12 AN: 225506 AF XY: 0.0000487

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000650

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000181

GnomAD4 exome AF: 0.0000104 AC: 15 AN: 1447742 Hom.: 0 Cov.: 31 AF XY: 0.0000111 AC XY: 8 AN XY: 719304

African (AFR) AF: 0.00 AC: 0 AN: 32936

American (AMR) AF: 0.00 AC: 0 AN: 42890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25866

East Asian (EAS) AF: 0.000334 AC: 13 AN: 38974

South Asian (SAS) AF: 0.00 AC: 0 AN: 83832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4588

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106986

Other (OTH) AF: 0.0000335 AC: 2 AN: 59712

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74498

African (AFR) AF: 0.00 AC: 0 AN: 41596

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000664 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.46
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.060
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.34	T
Polyphen		0.0010	B
Vest4		0.24
MutPred		0.18		Gain of catalytic residue at V9 (P = 0.026)
MVP		0.24
MPC		0.015
ClinPred		0.19	T
GERP RS		1.2
PromoterAI		0.071	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.13
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs201860851; hg19: chr14-35515750;