chr7-23691567-G-T

Variant names:

• chr7-23691567-G-T
• rs1282305046
• NM_199136.5:c.608G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_199136.5(FAM221A):​c.608G>T​(p.Gly203Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM221A NM_199136.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.33
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.769

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.608G>T	p.Gly203Val	missense	Exon 4 of 7	NP_954587.2	A4D161-1
	FAM221A	NM_001127364.3		c.608G>T	p.Gly203Val	missense	Exon 4 of 6	NP_001120836.1	A4D161-2
	FAM221A	NM_001300932.2		c.434G>T	p.Gly145Val	missense	Exon 3 of 6	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.608G>T	p.Gly203Val	missense	Exon 4 of 7	ENSP00000342576.4	A4D161-1
	FAM221A	ENST00000409192.7	TSL:1	c.608G>T	p.Gly203Val	missense	Exon 4 of 6	ENSP00000386927.3	A4D161-2
	FAM221A	ENST00000409994.3	TSL:1	c.434G>T	p.Gly145Val	missense	Exon 3 of 5	ENSP00000386631.3	A4D161-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.61	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		6.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.54		Gain of helix (P = 0.0325)
MVP		0.28
MPC		0.44
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.90
gMVP		0.85
Mutation Taster		=46/54	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: rs1282305046; hg19: chr7-23731186;