rs11556943

Variant names:

• chr1-40059450-C-A
• rs11556943
• NM_006367.4:c.104C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-40059450-C-A
• chr1-40059450-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006367.4(CAP1):​c.104C>A​(p.Pro35His) 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. 14/21 in silico tools predict a benign 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. P35L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAP1 NM_006367.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

Genes affected

CAP1 (HGNC:20040): (cyclase associated actin cytoskeleton regulatory protein 1) The protein encoded by this gene is related to the S. cerevisiae CAP protein, which is involved in the cyclic AMP pathway. The human protein is able to interact with other molecules of the same protein, as well as with CAP2 and actin. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089224875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAP1	NM_006367.4	c.104C>A	p.Pro35His	missense_variant	Exon 2 of 13	ENST00000372805.8	NP_006358.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAP1	ENST00000372805.8	c.104C>A	p.Pro35His	missense_variant	Exon 2 of 13	1	NM_006367.4	ENSP00000361891.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T;.;T;T;T;T;T;T;.;.;T;.;T;T;T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.82	.;.;T;T;T;T;T;.;.;T;T;T;T;T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.089	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L;L;.;.;.;.;.;L;L;L;L;.;.;.;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.6	N;D;N;N;N;N;N;N;D;D;N;D;N;N;D;N
REVEL	Benign	0.054
Sift	Benign	0.097	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;D
Sift4G	Uncertain	0.026	D;D;T;T;T;T;T;D;D;D;D;T;T;T;T;D
Polyphen		0.41	B;.;.;.;.;.;.;B;.;.;B;.;.;.;.;.
Vest4		0.10
MutPred		0.45		Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);Loss of glycosylation at P35 (P = 0.0323);
MVP		0.27
MPC		0.66
ClinPred		0.36	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.16
gMVP		0.24

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: rs11556943; hg19: chr1-40525122;