NM_001013647.2:c.1043C>G

Variant names:

• chr22-38607472-G-C
• NM_001013647.2:c.1043C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013647.2(FAM227A):​c.1043C>G​(p.Ser348Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,396,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM227A NM_001013647.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.184
• Publications: 0 publications found

Genes affected

FAM227A (HGNC:44197): (family with sequence similarity 227 member A)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10915148).

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.1043C>G	p.Ser348Cys	missense	Exon 12 of 17	NP_001013669.1	F5H4B4-1
	FAM227A	NM_001384270.1		c.776C>G	p.Ser259Cys	missense	Exon 12 of 17	NP_001371199.1
	FAM227A	NM_001291030.2		c.764C>G	p.Ser255Cys	missense	Exon 12 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.1043C>G	p.Ser348Cys	missense	Exon 12 of 17	ENSP00000445093.1	F5H4B4-1
	FAM227A	ENST00000355830.11	TSL:5	c.1043C>G	p.Ser348Cys	missense	Exon 12 of 19	ENSP00000348086.7	A0A0A0MRD0
	FAM227A	ENST00000540952.6	TSL:5	c.1043C>G	p.Ser348Cys	missense	Exon 12 of 17	ENSP00000493504.1	A0A2R8YCE3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1396158 Hom.: 0 Cov.: 29 AF XY: 0.00000290 AC XY: 2 AN XY: 688872

African (AFR) AF: 0.00 AC: 0 AN: 31552

American (AMR) AF: 0.00 AC: 0 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.00 AC: 0 AN: 35724

South Asian (SAS) AF: 0.00 AC: 0 AN: 79188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076038

Other (OTH) AF: 0.0000173 AC: 1 AN: 57886

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.064
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.9
DANN	Benign	0.61
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.18
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.048
Sift	Benign	0.10	T
Sift4G	Benign	0.20	T
Polyphen		0.92	P
Vest4		0.20
MutPred		0.25		Loss of phosphorylation at S348 (P = 0.0061)
MVP		0.014
ClinPred		0.47	T
GERP RS		0.23
Varity_R		0.055
Mutation Taster		=93/7	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

hg19: chr22-39003477; COSMIC: COSV63377961;