19-7608179-G-A

Variant names:

• chr19-7608179-G-A
• rs145801118
• NM_020902.2:c.675G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_020902.2(CAMSAP3):​c.675G>A​(p.Thr225Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,612,592 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0081 (20 hom., cov: 32)
  • Exomes 𝑓: 0.00082 (10 hom.)
• Consequence: CAMSAP3 NM_020902.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.87
• Publications: 1 publications found

Genes affected

CAMSAP3 (HGNC:29307): (calmodulin regulated spectrin associated protein family member 3) Enables actin filament binding activity and microtubule minus-end binding activity. Involved in several processes, including microtubule cytoskeleton organization; regulation of organelle organization; and zonula adherens maintenance. Located in cytoplasm; nucleoplasm; and zonula adherens. Colocalizes with centrosome and microtubule minus-end. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 19-7608179-G-A is Benign according to our data. Variant chr19-7608179-G-A is described in ClinVar as Benign. ClinVar VariationId is 775470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.86 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00813 (1239/152322) while in subpopulation AFR AF = 0.0267 (1108/41562). AF 95% confidence interval is 0.0254. There are 20 homozygotes in GnomAd4. There are 596 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1239 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020902.2. 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
	CAMSAP3	NM_020902.2	MANE Select	c.675G>A	p.Thr225Thr	synonymous	Exon 5 of 17	NP_065953.1	Q9P1Y5-1
	CAMSAP3	NM_001080429.3		c.756G>A	p.Thr252Thr	synonymous	Exon 7 of 19	NP_001073898.1	Q9P1Y5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMSAP3	ENST00000160298.9	TSL:2 MANE Select	c.675G>A	p.Thr225Thr	synonymous	Exon 5 of 17	ENSP00000160298.3	Q9P1Y5-1
	CAMSAP3	ENST00000446248.4	TSL:1	c.756G>A	p.Thr252Thr	synonymous	Exon 7 of 19	ENSP00000416797.1	Q9P1Y5-2
	CAMSAP3	ENST00000930508.1		c.675G>A	p.Thr225Thr	synonymous	Exon 5 of 17	ENSP00000600567.1

Frequencies

GnomAD3 genomes AF: 0.00811 AC: 1234 AN: 152204 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00908

GnomAD2 exomes AF: 0.00193 AC: 478 AN: 247460 AF XY: 0.00139

Gnomad AFR exome AF: 0.0269

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000279

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000895

Gnomad OTH exome AF: 0.000998

GnomAD4 exome AF: 0.000816 AC: 1192 AN: 1460270 Hom.: 10 Cov.: 31 AF XY: 0.000684 AC XY: 497 AN XY: 726464

African (AFR) AF: 0.0274 AC: 917 AN: 33480

American (AMR) AF: 0.00179 AC: 80 AN: 44720

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

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51942

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.0000468 AC: 52 AN: 1111914

Other (OTH) AF: 0.00210 AC: 127 AN: 60368

GnomAD4 genome AF: 0.00813 AC: 1239 AN: 152322 Hom.: 20 Cov.: 32 AF XY: 0.00800 AC XY: 596 AN XY: 74494

African (AFR) AF: 0.0267 AC: 1108 AN: 41562

American (AMR) AF: 0.00653 AC: 100 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68024

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.000401 Hom.: 0

Bravo AF: 0.0103

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.84
PhyloP100		-4.9
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs145801118; hg19: chr19-7673065;