4-99529903-A-C

Position:

• chr4-99529903-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_032149.3(C4orf17):​c.491A>C​(p.Asn164Thr) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C4orf17 NM_032149.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.10

Genes affected

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

C4orf17 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024040133).
• BP6: Variant 4-99529903-A-C is Benign according to our data. Variant chr4-99529903-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2242708.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C4orf17	NM_032149.3	c.491A>C	p.Asn164Thr	missense_variant	5/9	ENST00000326581.9	NP_115525.2
C4orf17	XM_011532315.3	c.491A>C	p.Asn164Thr	missense_variant	5/6		XP_011530617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C4orf17	ENST00000326581.9	c.491A>C	p.Asn164Thr	missense_variant	5/9	1	NM_032149.3	ENSP00000322582.4
C4orf17	ENST00000514652.5	c.491A>C	p.Asn164Thr	missense_variant	5/8	5		ENSP00000427663.1
C4orf17	ENST00000477187.1	n.491A>C		non_coding_transcript_exon_variant	5/10	2		ENSP00000423411.1
C4orf17	ENST00000503257.1	n.488A>C		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250392 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135388

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.13
DEOGEN2	Benign	0.00074	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.00089	T
MetaRNN	Benign	0.024	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.83	N;.
PROVEAN	Benign	0.23	N;N
REVEL	Benign	0.043
Sift	Benign	0.52	T;T
Sift4G	Benign	0.60	T;T
Polyphen		0.0020	B;.
Vest4		0.084
MutPred		0.15		Gain of phosphorylation at N164 (P = 0.0304);Gain of phosphorylation at N164 (P = 0.0304);
MVP		0.15
MPC		0.10
ClinPred		0.048	T
GERP RS		-0.63
Varity_R		0.029
gMVP		0.090

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

LitVar

Other links and lift over

dbSNP: rs1417597081; hg19: chr4-100451060;