FAM217A p.Val478Leu

Variant names:

• chr6-4068791-C-A
• NM_173563.3:c.1432G>T
• FAM217A p.Val478Leu

Your query was ambiguous. Multiple possible variants found:

• chr6-4068791-C-A
• chr6-4068791-C-G
• chr6-4068789-CAC-TAA
• chr6-4068789-CAC-AAG
• chr6-4068789-CAC-GAG
• chr6-4068789-CAC-TAG

Variant summary

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

The NM_173563.3(FAM217A):​c.1432G>T​(p.Val478Leu) 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. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM217A NM_173563.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07
• Publications: 0 publications found

Genes affected

FAM217A (HGNC:21362): (family with sequence similarity 217 member A)

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=0.047477126).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173563.3. 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
	FAM217A	NM_173563.3	MANE Select	c.1432G>T	p.Val478Leu	missense	Exon 7 of 7	NP_775834.2	Q8IXS0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM217A	ENST00000274673.8	TSL:1 MANE Select	c.1432G>T	p.Val478Leu	missense	Exon 7 of 7	ENSP00000274673.3	Q8IXS0
	FAM217A	ENST00000639338.1	TSL:5	c.1834G>T	p.Val612Leu	missense	Exon 9 of 9	ENSP00000492773.1	A0A1W2PRP4
	FAM217A	ENST00000380188.2	TSL:2	n.1841G>T		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.4
DANN	Benign	0.86
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.46	N
PhyloP100		2.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.039
Sift	Benign	0.75	T
Sift4G	Benign	0.49	T
Varity_R		0.033
gMVP		0.027
Mutation Taster		=100/0	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

hg19: chr6-4069025;