chr4-99522563-G-C

Variant names:

• chr4-99522563-G-C
• rs13143848
• NM_032149.3:c.191G>C

Variant summary

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

The NM_032149.3(C4orf17):​c.191G>C​(p.Gly64Ala) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: C4orf17 NM_032149.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 24 publications found

Genes affected

C4orf17 (HGNC:25274): (chromosome 4 open reading frame 17)

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=0.10032573).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032149.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C4orf17	NM_032149.3	MANE Select	c.191G>C	p.Gly64Ala	missense	Exon 3 of 9	NP_115525.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C4orf17	ENST00000326581.9	TSL:1 MANE Select	c.191G>C	p.Gly64Ala	missense	Exon 3 of 9	ENSP00000322582.4
	C4orf17	ENST00000514652.5	TSL:5	c.191G>C	p.Gly64Ala	missense	Exon 3 of 8	ENSP00000427663.1
	C4orf17	ENST00000477187.1	TSL:2	n.191G>C		non_coding_transcript_exon	Exon 3 of 10	ENSP00000423411.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 35251

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.5
DANN	Benign	0.96
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.11
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.048
Sift	Benign	0.39	T
Sift4G	Benign	0.33	T
Polyphen		0.76	P
Vest4		0.21
MutPred		0.31		Loss of sheet (P = 0.0315)
MVP		0.13
MPC		0.20
ClinPred		0.16	T
GERP RS		1.2
Varity_R		0.037
gMVP		0.18
Mutation Taster		=99/1	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: rs13143848; hg19: chr4-100443720;