chr6-25600522-G-A

Position:

• chr6-25600522-G-A

Variant summary

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

The NM_017640.6(CARMIL1):​c.3328G>A​(p.Asp1110Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CARMIL1 NM_017640.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66

Genes affected

CARMIL1 (HGNC:21581): (capping protein regulator and myosin 1 linker 1) Involved in several processes, including actin filament network formation; plasma membrane bounded cell projection organization; and positive regulation of cellular component organization. Located in several cellular components, including lamellipodium; macropinosome; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

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=0.12453735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARMIL1	NM_017640.6	c.3328G>A	p.Asp1110Asn	missense_variant	33/37	ENST00000329474.7	NP_060110.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARMIL1	ENST00000329474.7	c.3328G>A	p.Asp1110Asn	missense_variant	33/37	1	NM_017640.6	ENSP00000331983	P1
CARMIL1	ENST00000700669.1	c.3328G>A	p.Asp1110Asn	missense_variant	33/37			ENSP00000515137
CARMIL1	ENST00000635618.1	c.2128G>A	p.Asp710Asn	missense_variant, NMD_transcript_variant	20/26	5		ENSP00000489114

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.3328G>A (p.D1110N) alteration is located in exon 33 (coding exon 33) of the CARMIL1 gene. This alteration results from a G to A substitution at nucleotide position 3328, causing the aspartic acid (D) at amino acid position 1110 to be replaced by an asparagine (N). 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	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.040
Eigen_PC	Benign	0.077
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.91	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.12
Sift	Uncertain	0.018	D
Sift4G	Benign	0.36	T
Polyphen		0.14	B
Vest4		0.061
MutPred		0.24		Gain of MoRF binding (P = 0.0421);
MVP		0.45
MPC		0.31
ClinPred		0.49	T
GERP RS		5.2
Varity_R		0.095
gMVP		0.085

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-25600750;