NM_198491.3:c.607G>T

Variant names:

• chr16-85102258-C-A
• rs369997578
• NM_198491.3:c.607G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_198491.3(CIBAR2):​c.607G>T​(p.Ala203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. A203T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CIBAR2 NM_198491.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 0 publications found

Genes affected

CIBAR2 (HGNC:24781): (CBY1 interacting BAR domain containing 2) Predicted to be involved in cilium assembly. Predicted to be located in centriole and cytoplasm. Predicted to be active in ciliary basal body and ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.935

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR2	NM_198491.3	c.607G>T	p.Ala203Ser	missense_variant	Exon 7 of 9	ENST00000539556.6	NP_940893.1
CIBAR2	NM_001366920.1	c.607G>T	p.Ala203Ser	missense_variant	Exon 7 of 9		NP_001353849.1
CIBAR2	XM_011523063.2	c.607G>T	p.Ala203Ser	missense_variant	Exon 7 of 10		XP_011521365.1
CIBAR2	XM_017023198.2	c.607G>T	p.Ala203Ser	missense_variant	Exon 7 of 10		XP_016878687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR2	ENST00000539556.6	c.607G>T	p.Ala203Ser	missense_variant	Exon 7 of 9	5	NM_198491.3	ENSP00000443411.1
CIBAR2	ENST00000618669.3	c.322G>T	p.Ala108Ser	missense_variant	Exon 5 of 7	5		ENSP00000478373.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461100 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726938

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111338

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	.;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Uncertain	0.080	D
MutationAssessor	Pathogenic	3.2	.;M
PhyloP100		1.2
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.3	N;.
REVEL	Uncertain	0.35
Sift	Uncertain	0.0080	D;.
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	.;D
Vest4		0.65
MutPred		0.80		Gain of disorder (P = 0.0259);Gain of disorder (P = 0.0259);
MVP		0.42
MPC		0.25
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.22
gMVP		0.099
Mutation Taster		=85/15	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: rs369997578; hg19: chr16-85135864;