NM_001099858.2:c.665T>C

Variant names:

• chr7-42910236-A-G
• NM_001099858.2:c.665T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099858.2(C7orf25):​c.665T>C​(p.Val222Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: C7orf25 NM_001099858.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13
• Publications: 0 publications found

Genes affected

C7orf25 (HGNC:21703): (chromosome 7 open reading frame 25)

ENSG00000256646 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14223969).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099858.2. 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
	C7orf25	NM_001099858.2	MANE Select	c.665T>C	p.Val222Ala	missense	Exon 2 of 2	NP_001093328.2	Q9BPX7-1
	C7orf25	NM_001363436.1		c.665T>C	p.Val222Ala	missense	Exon 2 of 2	NP_001350365.1	Q9BPX7-1
	C7orf25	NM_024054.3		c.665T>C	p.Val222Ala	missense	Exon 2 of 2	NP_076959.2	Q9BPX7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7orf25	ENST00000350427.5	TSL:2 MANE Select	c.665T>C	p.Val222Ala	missense	Exon 2 of 2	ENSP00000343364.4	Q9BPX7-1
	C7orf25	ENST00000447342.5	TSL:2	c.839T>C	p.Val280Ala	missense	Exon 2 of 2	ENSP00000413029.2	Q9BPX7-2
	C7orf25	ENST00000438029.1	TSL:2	c.665T>C	p.Val222Ala	missense	Exon 2 of 2	ENSP00000396597.1	Q9BPX7-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.040
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		7.1
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.093
Sift	Benign	0.54	T
Sift4G	Benign	0.27	T
Polyphen		0.0020	B
Vest4		0.077
MutPred		0.61		Gain of disorder (P = 0.0608)
MVP		0.38
MPC		0.32
ClinPred		0.39	T
GERP RS		4.6
Varity_R		0.052
gMVP		0.51
Mutation Taster		=59/41	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: chr7-42949835;