NM_001013647.2:c.1006C>G

Variant names:

• chr22-38620244-G-C
• rs1028758884
• NM_001013647.2:c.1006C>G

Variant summary

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

The NM_001013647.2(FAM227A):​c.1006C>G​(p.Pro336Ala) 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. 16/19 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. P336T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM227A NM_001013647.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61
• Publications: 0 publications found

Genes affected

FAM227A (HGNC:44197): (family with sequence similarity 227 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=0.040148705).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013647.2. 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
	FAM227A	NM_001013647.2	MANE Select	c.1006C>G	p.Pro336Ala	missense	Exon 11 of 17	NP_001013669.1	F5H4B4-1
	FAM227A	NM_001384270.1		c.739C>G	p.Pro247Ala	missense	Exon 11 of 17	NP_001371199.1
	FAM227A	NM_001291030.2		c.727C>G	p.Pro243Ala	missense	Exon 11 of 17	NP_001277959.1	F5H4B4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227A	ENST00000535113.7	TSL:5 MANE Select	c.1006C>G	p.Pro336Ala	missense	Exon 11 of 17	ENSP00000445093.1	F5H4B4-1
	FAM227A	ENST00000355830.11	TSL:5	c.1006C>G	p.Pro336Ala	missense	Exon 11 of 19	ENSP00000348086.7	A0A0A0MRD0
	FAM227A	ENST00000540952.6	TSL:5	c.1006C>G	p.Pro336Ala	missense	Exon 11 of 17	ENSP00000493504.1	A0A2R8YCE3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.074
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.0040
DANN	Benign	0.16
DEOGEN2	Benign	0.00037	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0051	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		-2.6
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.14
Sift	Benign	0.67	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.078
MutPred		0.23		Loss of loop (P = 0.0073)
MVP		0.014
ClinPred		0.035	T
GERP RS		-6.0
Varity_R		0.012
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1028758884; hg19: chr22-39016249;