9-135818051-G-A

Variant names:

• chr9-135818051-G-A
• rs41309387
• NM_015447.4:c.4197C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_015447.4(CAMSAP1):​c.4197C>T​(p.Gly1399Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00788 in 1,613,798 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0080 (63 hom.)
• Consequence: CAMSAP1 NM_015447.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.03
• Publications: 3 publications found

Genes affected

CAMSAP1 (HGNC:19946): (calmodulin regulated spectrin associated protein 1) Enables microtubule minus-end binding activity and spectrin binding activity. Involved in several processes, including neuron projection development; regulation of cell morphogenesis; and regulation of microtubule polymerization. Located in microtubule. Colocalizes with microtubule minus-end. [provided by Alliance of Genome Resources, Apr 2022]

CAMSAP1 Gene-Disease associations (from GenCC):

• cortical dysplasia, complex, with other brain malformations 12

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 9-135818051-G-A is Benign according to our data. Variant chr9-135818051-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 788825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.03 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015447.4. 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
	CAMSAP1	NM_015447.4	MANE Select	c.4197C>T	p.Gly1399Gly	synonymous	Exon 14 of 17	NP_056262.3	Q5T5Y3-1
	CAMSAP1	NM_001437279.1		c.4230C>T	p.Gly1410Gly	synonymous	Exon 15 of 18	NP_001424208.1
	CAMSAP1	NM_001437280.1		c.3765C>T	p.Gly1255Gly	synonymous	Exon 13 of 16	NP_001424209.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMSAP1	ENST00000389532.9	TSL:5 MANE Select	c.4197C>T	p.Gly1399Gly	synonymous	Exon 14 of 17	ENSP00000374183.4	Q5T5Y3-1
	CAMSAP1	ENST00000312405.10	TSL:1	c.3363C>T	p.Gly1121Gly	synonymous	Exon 12 of 15	ENSP00000312463.6	Q5T5Y3-2
	CAMSAP1	ENST00000409386.3	TSL:5	c.4230C>T	p.Gly1410Gly	synonymous	Exon 15 of 18	ENSP00000386420.3	Q5T5Y3-3

Frequencies

GnomAD3 genomes AF: 0.00632 AC: 962 AN: 152202 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00171

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00844

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00976

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00629 AC: 1570 AN: 249704 AF XY: 0.00633

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00741

Gnomad ASJ exome AF: 0.0165

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00116

Gnomad NFE exome AF: 0.00879

Gnomad OTH exome AF: 0.00755

GnomAD4 exome AF: 0.00804 AC: 11751 AN: 1461478 Hom.: 63 Cov.: 31 AF XY: 0.00788 AC XY: 5731 AN XY: 727024

African (AFR) AF: 0.00137 AC: 46 AN: 33480

American (AMR) AF: 0.00774 AC: 346 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 400 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00263 AC: 227 AN: 86256

European-Finnish (FIN) AF: 0.00165 AC: 88 AN: 53222

Middle Eastern (MID) AF: 0.00936 AC: 54 AN: 5768

European-Non Finnish (NFE) AF: 0.00907 AC: 10086 AN: 1111842

Other (OTH) AF: 0.00833 AC: 503 AN: 60362

GnomAD4 genome AF: 0.00631 AC: 961 AN: 152320 Hom.: 3 Cov.: 33 AF XY: 0.00603 AC XY: 449 AN XY: 74474

African (AFR) AF: 0.00171 AC: 71 AN: 41588

American (AMR) AF: 0.00843 AC: 129 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00976 AC: 664 AN: 68022

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.00911 Hom.: 6

Bravo AF: 0.00720

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0113

EpiControl AF: 0.0109

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.0
DANN	Benign	0.62
PhyloP100		1.0
Mutation Taster		=99/1	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: rs41309387; hg19: chr9-138709897; COSMIC: COSV100409483;