NM_139320.2:c.290T>A

Variant names:

• chr15-30373016-A-T
• NM_139320.2:c.290T>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_139320.2(CHRFAM7A):​c.290T>A​(p.Ile97Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: CHRFAM7A NM_139320.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.20

Genes affected

CHRFAM7A (HGNC:15781): (CHRNA7 (exons 5-10) and FAM7A (exons A-E) fusion) The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The family member CHRNA7, which is located on chromosome 15 in a region associated with several neuropsychiatric disorders, is partially duplicated and forms a hybrid with a novel gene from the family with sequence similarity 7 (FAM7A). Alternative splicing has been observed, and two variants exist, for this hybrid gene. The N-terminally truncated products predicted by the largest open reading frames for each variant would lack the majority of the neurotransmitter-gated ion-channel ligand binding domain but retain the transmembrane region that forms the ion channel. Although current evidence supports transcription of this hybrid gene, translation of the nicotinic acetylcholine receptor-like protein-encoding open reading frames has not been confirmed. [provided by RefSeq, Jul 2008]

LOC105370751 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.804

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRFAM7A	NM_139320.2	c.290T>A	p.Ile97Asn	missense_variant	Exon 6 of 10	ENST00000299847.7	NP_647536.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRFAM7A	ENST00000299847.7	c.290T>A	p.Ile97Asn	missense_variant	Exon 6 of 10	1	NM_139320.2	ENSP00000299847.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;.;.;.
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Pathogenic	1.0	D;D;.;D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.80	D;D;D;D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Uncertain	2.3	M;.;.;.
PROVEAN	Pathogenic	-5.5	D;D;D;D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;.
Polyphen		0.97	D;.;.;.
Vest4		0.83
MutPred		0.67		Gain of disorder (P = 0.0092);.;.;Gain of disorder (P = 0.0092);
MVP		0.75
ClinPred		0.99	D
GERP RS		2.1
Varity_R		0.76
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr15-30665219;