7-23689336-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM221A	NM_199136.5	c.307G>C	p.Val103Leu	missense_variant	Exon 3 of 7	ENST00000344962.9	NP_954587.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM221A	ENST00000344962.9	c.307G>C	p.Val103Leu	missense_variant	Exon 3 of 7	1	NM_199136.5	ENSP00000342576.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.307G>C (p.V103L) alteration is located in exon 3 (coding exon 3) of the FAM221A gene. This alteration results from a G to C substitution at nucleotide position 307, causing the valine (V) at amino acid position 103 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.72	D;D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.8	M;M;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.059	T;D;T;D
Sift4G	Uncertain	0.017	D;D;D;D
Polyphen		0.98	D;D;.;P
Vest4		0.72
MutPred		0.32		Loss of catalytic residue at V103 (P = 0.0661);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-23728955;