6-4069072-A-G

Variant names:

• chr6-4069072-A-G
• rs1769215499
• NM_173563.3:c.1151T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_173563.3(FAM217A):​c.1151T>C​(p.Leu384Pro) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM217A NM_173563.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.762
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029172689).
• BP6: Variant 6-4069072-A-G is Benign according to our data. Variant chr6-4069072-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3092279.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1151T>C	p.Leu384Pro	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.1151T>C	p.Leu384Pro	missense	Exon 7 of 7	ENSP00000274673.3	Q8IXS0
	FAM217A	ENST00000639338.1	TSL:5	c.1553T>C	p.Leu518Pro	missense	Exon 9 of 9	ENSP00000492773.1	A0A1W2PRP4
	FAM217A	ENST00000380188.2	TSL:2	n.1560T>C		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.046
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.5
DANN	Benign	0.45
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00080	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.3	N
PhyloP100		0.76
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.038
Sift	Benign	0.22	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.024
MutPred		0.28		Gain of relative solvent accessibility (P = 0.0023)
MVP		0.040
MPC		0.039
ClinPred		0.089	T
GERP RS		0.53
Varity_R		0.089
gMVP		0.024
Mutation Taster		=95/5	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

Other links and lift over

dbSNP: rs1769215499; hg19: chr6-4069306;