NM_199136.5:c.790G>A

Variant names:

• chr7-23700830-G-A
• rs1424916816
• NM_199136.5:c.790G>A

Variant summary

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

The NM_199136.5(FAM221A):​c.790G>A​(p.Asp264Asn) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM221A NM_199136.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• 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.790G>A	p.Asp264Asn	missense	Exon 6 of 7	NP_954587.2	A4D161-1
	FAM221A	NM_001127364.3		c.682G>A	p.Asp228Asn	missense	Exon 5 of 6	NP_001120836.1	A4D161-2
	FAM221A	NM_001300932.2		c.616G>A	p.Asp206Asn	missense	Exon 5 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.790G>A	p.Asp264Asn	missense	Exon 6 of 7	ENSP00000342576.4	A4D161-1
	FAM221A	ENST00000409192.7	TSL:1	c.682G>A	p.Asp228Asn	missense	Exon 5 of 6	ENSP00000386927.3	A4D161-2
	FAM221A	ENST00000409994.3	TSL:1	c.508G>A	p.Asp170Asn	missense	Exon 4 of 5	ENSP00000386631.3	A4D161-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.047	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.16
Sift	Benign	0.030	D
Sift4G	Uncertain	0.020	D
Polyphen		0.90	P
Vest4		0.61
MutPred		0.30		Gain of MoRF binding (P = 0.0522)
MVP		0.41
MPC		0.41
ClinPred		0.94	D
GERP RS		6.0
Varity_R		0.16
gMVP		0.33
Mutation Taster		=75/25	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: rs1424916816; hg19: chr7-23740449;