NM_198491.3:c.607G>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_198491.3(CIBAR2):​c.607G>A​(p.Ala203Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,613,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: CIBAR2 NM_198491.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.24
• Publications: 3 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.41469914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR2	NM_198491.3	c.607G>A	p.Ala203Thr	missense_variant	Exon 7 of 9	ENST00000539556.6	NP_940893.1
CIBAR2	NM_001366920.1	c.607G>A	p.Ala203Thr	missense_variant	Exon 7 of 9		NP_001353849.1
CIBAR2	XM_011523063.2	c.607G>A	p.Ala203Thr	missense_variant	Exon 7 of 10		XP_011521365.1
CIBAR2	XM_017023198.2	c.607G>A	p.Ala203Thr	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>A	p.Ala203Thr	missense_variant	Exon 7 of 9	5	NM_198491.3	ENSP00000443411.1
CIBAR2	ENST00000618669.3	c.322G>A	p.Ala108Thr	missense_variant	Exon 5 of 7	5		ENSP00000478373.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000676 AC: 17 AN: 251486 AF XY: 0.0000809

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000121 AC: 177 AN: 1461094 Hom.: 0 Cov.: 29 AF XY: 0.000111 AC XY: 81 AN XY: 726936

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: 0.0000116 AC: 1 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: 0.000156 AC: 173 AN: 1111332

Other (OTH) AF: 0.0000497 AC: 3 AN: 60356

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152092 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74278

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.0000579 Hom.: 0

Bravo AF: 0.0000567

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000906 AC: 11

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.607G>A (p.A203T) alteration is located in exon 7 (coding exon 7) of the FAM92B gene. This alteration results from a G to A substitution at nucleotide position 607, causing the alanine (A) at amino acid position 203 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.8	.;L
PhyloP100		1.2
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.0	D;.
REVEL	Benign	0.21
Sift	Benign	0.17	T;.
Sift4G	Uncertain	0.036	D;D
Polyphen		0.99	.;D
Vest4		0.36
MVP		0.43
MPC		0.18
ClinPred		0.65	D
GERP RS		4.8
Varity_R		0.20
gMVP		0.13
Mutation Taster		=76/24	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;