15-30362661-T-G

Variant names:

• chr15-30362661-T-G
• rs2058751485
• NM_139320.2:c.871A>C

Variant summary

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

The NM_139320.2(CHRFAM7A):​c.871A>C​(p.Asn291His) variant causes a missense change involving the alteration of a conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N291D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 1)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHRFAM7A NM_139320.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.33
• Publications: 0 publications found

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]

LINC02249 (HGNC:32351): (long intergenic non-protein coding RNA 2249)

LOC105370751 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139320.2. 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
	CHRFAM7A	NM_139320.2	MANE Select	c.871A>C	p.Asn291His	missense	Exon 10 of 10	NP_647536.1	Q494W8
	CHRFAM7A	NM_148911.1		c.598A>C	p.Asn200His	missense	Exon 9 of 9	NP_683709.1	P36544

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRFAM7A	ENST00000299847.7	TSL:1 MANE Select	c.871A>C	p.Asn291His	missense	Exon 10 of 10	ENSP00000299847.3	Q494W8
	CHRFAM7A	ENST00000401522.7	TSL:1	c.598A>C	p.Asn200His	missense	Exon 11 of 11	ENSP00000385389.3	A0A0A6YYA8
	CHRFAM7A	ENST00000853243.1		c.871A>C	p.Asn291His	missense	Exon 11 of 11	ENSP00000523302.1

Frequencies

GnomAD3 genomes Cov.: 1

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 331318 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 173740

African (AFR) AF: 0.00 AC: 0 AN: 12296

American (AMR) AF: 0.00 AC: 0 AN: 11936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9672

East Asian (EAS) AF: 0.00 AC: 0 AN: 21062

South Asian (SAS) AF: 0.00 AC: 0 AN: 41060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1480

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 194538

Other (OTH) AF: 0.00 AC: 0 AN: 19330

GnomAD4 genome Cov.: 1

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Uncertain	0.015	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.3
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.42
Sift	Benign	0.22	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.36		Gain of sheet (P = 0.0477)
MVP		0.61
ClinPred		0.92	D
GERP RS		3.1
Varity_R		0.10
gMVP		0.48
Mutation Taster		=84/16	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

dbSNP: rs2058751485; hg19: chr15-30654864;