NM_173607.5:c.659A>C

Variant names:

• chr14-35081176-A-C
• NM_173607.5:c.659A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173607.5(FAM177A1):​c.659A>C​(p.Asp220Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM177A1 NM_173607.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67

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]

LOC101927178 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18023396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM177A1	NM_173607.5	c.659A>C	p.Asp220Ala	missense_variant	Exon 5 of 5	ENST00000280987.9	NP_775878.2
FAM177A1	NM_001079519.1	c.590A>C	p.Asp197Ala	missense_variant	Exon 7 of 7		NP_001072987.1
FAM177A1	NM_001289022.3	c.590A>C	p.Asp197Ala	missense_variant	Exon 6 of 6		NP_001275951.1
LOC101927178	NR_110415.1	n.96A>C		non_coding_transcript_exon_variant	Exon 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM177A1	ENST00000280987.9	c.659A>C	p.Asp220Ala	missense_variant	Exon 5 of 5	1	NM_173607.5	ENSP00000280987.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.659A>C (p.D220A) alteration is located in exon 5 (coding exon 5) of the FAM177A1 gene. This alteration results from a A to C substitution at nucleotide position 659, causing the aspartic acid (D) at amino acid position 220 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T;T;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.66	T;.;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.067
Sift	Uncertain	0.018	D;D;D
Sift4G	Uncertain	0.040	D;D;D
Polyphen		0.26	B;B;P
Vest4		0.36
MutPred		0.24		Gain of catalytic residue at F192 (P = 0.0084);Gain of catalytic residue at F192 (P = 0.0084);.;
MVP		0.69
MPC		0.030
ClinPred		0.92	D
GERP RS		5.0
Varity_R		0.11
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-35550382;