NM_199136.5:c.307G>C

Variant names:

• chr7-23689336-G-C
• NM_199136.5:c.307G>C

Variant summary

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

The NM_199136.5(FAM221A):​c.307G>C​(p.Val103Leu) 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: 9.38
• 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.307G>C	p.Val103Leu	missense	Exon 3 of 7	NP_954587.2	A4D161-1
	FAM221A	NM_001127364.3		c.307G>C	p.Val103Leu	missense	Exon 3 of 6	NP_001120836.1	A4D161-2
	FAM221A	NM_001300932.2		c.133G>C	p.Val45Leu	missense	Exon 2 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.307G>C	p.Val103Leu	missense	Exon 3 of 7	ENSP00000342576.4	A4D161-1
	FAM221A	ENST00000409192.7	TSL:1	c.307G>C	p.Val103Leu	missense	Exon 3 of 6	ENSP00000386927.3	A4D161-2
	FAM221A	ENST00000409994.3	TSL:1	c.133G>C	p.Val45Leu	missense	Exon 2 of 5	ENSP00000386631.3	A4D161-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.36
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		9.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.20
Sift	Benign	0.059	T
Sift4G	Uncertain	0.017	D
Polyphen		0.98	D
Vest4		0.72
MutPred		0.32		Loss of catalytic residue at V103 (P = 0.0661)
MVP		0.31
MPC		0.21
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.23
gMVP		0.40
Mutation Taster		=62/38	polymorphism

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

hg19: chr7-23728955;