6-25279805-G-A

Variant names:

• chr6-25279805-G-A
• rs1412088464
• NM_017640.6:c.10G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017640.6(CARMIL1):​c.10G>A​(p.Glu4Lys) 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. 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. E4Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CARMIL1 NM_017640.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92
• Publications: 0 publications found

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]

CMAHP (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17397809).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017640.6. 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
	CARMIL1	NM_017640.6	MANE Select	c.10G>A	p.Glu4Lys	missense	Exon 1 of 37	NP_060110.4
	CARMIL1	NM_001173977.2		c.10G>A	p.Glu4Lys	missense	Exon 1 of 37	NP_001167448.1	A0A8V8TRE2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARMIL1	ENST00000329474.7	TSL:1 MANE Select	c.10G>A	p.Glu4Lys	missense	Exon 1 of 37	ENSP00000331983.6	Q5VZK9-1
	CARMIL1	ENST00000461945.1	TSL:1	c.-210+566G>A		intron	N/A	ENSP00000489403.1	A0A0U1RR91
	CARMIL1	ENST00000865798.1		c.10G>A	p.Glu4Lys	missense	Exon 1 of 38	ENSP00000535857.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	0.094
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.16
Sift	Uncertain	0.019	D
Sift4G	Benign	0.21	T
Polyphen		0.95	P
Vest4		0.43
MutPred		0.12		Gain of ubiquitination at E4 (P = 0.0085)
MVP		0.068
MPC		0.89
ClinPred		0.96	D
GERP RS		4.2
PromoterAI		0.058	Neutral
Varity_R		0.34
gMVP		0.50
Mutation Taster		=268/32	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: rs1412088464; hg19: chr6-25280033;