chr7-23684573-C-G

Variant names:

• chr7-23684573-C-G
• rs752705562
• NM_199136.5:c.140C>G

Variant summary

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

The NM_199136.5(FAM221A):​c.140C>G​(p.Pro47Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P47L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM221A NM_199136.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.62
• Publications: 0 publications found

Genes affected

FAM221A (HGNC:27977): (family with sequence similarity 221 member A)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199136.5. 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
	FAM221A	NM_199136.5	MANE Select	c.140C>G	p.Pro47Arg	missense	Exon 2 of 7	NP_954587.2	A4D161-1
	FAM221A	NM_001127364.3		c.140C>G	p.Pro47Arg	missense	Exon 2 of 6	NP_001120836.1	A4D161-2
	FAM221A	NM_001300932.2		c.65+4290C>G		intron	N/A	NP_001287861.1	B8ZZQ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM221A	ENST00000344962.9	TSL:1 MANE Select	c.140C>G	p.Pro47Arg	missense	Exon 2 of 7	ENSP00000342576.4	A4D161-1
	FAM221A	ENST00000409192.7	TSL:1	c.140C>G	p.Pro47Arg	missense	Exon 2 of 6	ENSP00000386927.3	A4D161-2
	FAM221A	ENST00000409994.3	TSL:1	c.65+4290C>G		intron	N/A	ENSP00000386631.3	A4D161-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.26
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.35		Gain of MoRF binding (P = 0.0088)
MVP		0.26
MPC		0.44
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.55
gMVP		0.72
Mutation Taster		=16/84	disease causing

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: rs752705562; hg19: chr7-23724192;