1-179814065-C-T

Variant names:

• chr1-179814065-C-T
• rs1420641997
• NM_173509.3:c.380C>T
• FAM163A p.Thr127Ile

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173509.3(FAM163A):​c.380C>T​(p.Thr127Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. T127R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM163A NM_173509.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 0 publications found

Genes affected

FAM163A (HGNC:28274): (family with sequence similarity 163 member A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000297013 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049511015).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173509.3. 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
	FAM163A	NM_173509.3	MANE Select	c.380C>T	p.Thr127Ile	missense	Exon 5 of 5	NP_775780.1	Q96GL9
	FAM163A	NM_001329712.2		c.380C>T	p.Thr127Ile	missense	Exon 5 of 5	NP_001316641.1	Q96GL9
	FAM163A	NM_001329713.2		c.380C>T	p.Thr127Ile	missense	Exon 6 of 6	NP_001316642.1	Q96GL9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM163A	ENST00000341785.5	TSL:1 MANE Select	c.380C>T	p.Thr127Ile	missense	Exon 5 of 5	ENSP00000354891.4	Q96GL9
	FAM163A	ENST00000879738.1		c.380C>T	p.Thr127Ile	missense	Exon 5 of 5	ENSP00000549797.1
	FAM163A	ENST00000879739.1		c.380C>T	p.Thr127Ile	missense	Exon 5 of 5	ENSP00000549798.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.39
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.70
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.037
Sift	Benign	0.63	T
Sift4G	Benign	0.48	T
Varity_R		0.070
gMVP		0.56
Mutation Taster		=74/26	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1420641997;

hg19: chr1-179783200;